LymphomaPhase 1/2NCT02257567
A Study of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab Plus Bendamustine in Participants With Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
A Phase 1/2 study testing Bendamustine, Obinutuzumab and Polatuzumab vedotin (Liquid) in people with Lymphoma, run by Hoffmann-La Roche at 62 sites in 13 countries.
Trial summary
This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- Bendamustine, Obinutuzumab and Polatuzumab vedotin (Liquid)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 331 participants
- Where
- 62 sitesin 13 countries
- Study dates
- 15 Oct 2014to 21 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or refractory DLBCL
- If the participant has received prior bendamustine, response duration must have been greater than (>) 1 year (for participants who have relapse disease after a prior regimen)
- At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 centimeters (cm) in its longest dimension
- Confirmed availability of archival or freshly collected tumor tissue
- The Phase II NF Cohorts (Arms G and H) will be required to submit tissue and pathology report for central pathology review.
- Life expectancy of at least 24 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Adequate hematological function unless inadequate function is due to underlying disease
Who cannot join
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs, or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
- Contraindication to bendamustine, rituximab, or obinutuzumab
- Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4 weeks or 5 half-lives before Cycle 1 Day 1
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1 Day 1
- Ongoing corticosteroid use >30 mg per day prednisone or equivalent, for purposes other than lymphoma symptom control
- Completion of autologous stem cell transplant (SCT) within 100 days prior to Cycle 1 Day 1
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- Prior allogeneic SCT
- Eligibility for autologous SCT
- Grade 3b FL
- History of transformation of indolent disease to DLBCL
- Primary or secondary CNS lymphoma
- Current Grade >1 peripheral neuropathy
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to Cycle 1 Day 1
- Suspected or latent tuberculosis
- Positive test results for chronic hepatitis B virus (HBV) infection or for hepatitis C virus (HCV) antibody
- Known history of human immunodeficiency virus (HIV) seropositive status or known infection with human T-cell leukemia virus 1 (HTLV-1) virus
- Women who are pregnant or lactating or who intend to become pregnant within a year of the last dose of study treatment in the rituximab cohort or within 18 months of last dose in the obinutuzumab cohort
- Evidence of laboratory abnormalities in standard renal, hepatic, or coagulation function tests
- Treatment with chimeric antigen receptor T-cell therapy within 100 days prior to Cycle 1, Day 1
Trial locations and contacts
62 sites in 13 countries.
62 sites in 13 countries
United States16 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87131
Emory Univ Winship Cancer Inst
Atlanta, Georgia, 30322
Univ of Colorado Canc Ctr
Aurora, Colorado, 80045
Weinberg CA Inst Franklin Sq
Baltimore, Maryland, 21237
University of Alabama at Birmingham
Birmingham, Alabama, 35294-3300
Levine Cancer Institute
Charlotte, North Carolina, 28204
City of Hope National Medical Center
Duarte, California, 91010
West Clinic
Germantown, Tennessee, 38138
Clearview Cancer Institute
Huntsville, Alabama, 35805
Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)
Jacksonville, Florida, 32256
Joliet Oncology-Hematology; Associates, Ltd.
Joliet, Illinois, 60435
Horizon Oncology Research, Inc.
Lafayette, Indiana, 47905
Regional Cancer Care Associates LLC - Morristown
Morristown, New Jersey, 07962
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Swedish Cancer Inst.
Seattle, Washington, 98104
Northwest Medical Specialties
Tacoma, Washington, 98405
France6 sites
Chu Site Du Bocage;Hematologie Clinique
Dijon, 21079
Centre Hospitalier Departemental Les Oudairies
La Roche-sur-Yon, 85925
Centre Leon Berard; Departement Oncologie Medicale
Lyon, 69373
CHU Saint Eloi; Service d'Hématologie Clinique
Montpellier, 34295
CHU Lyon Sud - Service Hématologie
Pierre-Bénite, 69310
Centre Henri Becquerel; Hematologie
Rouen, 76038
Germany5 sites
HELIOS Klinikum Erfurt - Innere Medizin - 4. Medizinische Klinik, Hämatologie
Erfurt, 99089
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Abt. für Hämatologie und Onkologie
Mainz, 55131
Joh. Wesling Klinikum Minden; Klinik fuer Hämatologie und Onkologie
Minden, 32429
Gemeinschaftspraxis für Hämatologie und Onkologie
Münster, 48153
Klinik der Uni Regensburg; Hämatologie/Onkologie, Studienzentrale
Regensburg, 93053
Spain5 sites
Hospital Universitari Vall d'Hebron; Servicio de Hematologia
Barcelona, 08035
Hospital Clinic i Provincial de Barcelona; Hematology
Barcelona, 08036
Hospital Universitario la Paz; Servicio de Hematologia
Madrid, 28046
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
Salamanca, 37007
Hospital Universitario Virgen del Rocio; Servicio de Hematologia
Seville, 41013
Australia4 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Monash Medical Centre; Haematology Research
Clayton, Victoria, 3168
Adelaide Cancer Centre
Kurralta Park, South Australia, 5037
Prince of Wales Hospital; Oncology
Randwick, New South Wales, 2031
Canada4 sites
Queen Elizabeth II Health Sciences Centre; Oncology
Halifax, Nova Scotia, B3H 2Y9
Hopital Maisonneuve- Rosemont; Oncology
Montreal, Quebec, H1T 2M4
Jewish General Hospital
Montreal, Quebec, H3T 1E2
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
Czechia4 sites
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
Brno, 625 00
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05
Fakultní nemocnice Ostrava Klinika hematoonkologie
Ostrava, 70852
I Interni klinika; Vseobecna fakultni nemocnice
Prague, 128 08
Italy4 sites
Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
Alessandria, Piedmont, 15121
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
Brescia, Lombardy, 25123
Irccs Istituto Europeo Di Oncologia (IEO); Emato-Oncologia
Milan, Lombardy, 20141
Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
Naples, Campania, 80131
Turkey (Türkiye)4 sites
Ankara University; Hematology
Ankara, 06620
Dokuz Eylul Uni ; Hematology
Izmir, 35100
Ondokuzmayis University Medical Faculty Heamatology Department
Samsun, 55139
Karadeniz Technical Uni School of Medicine; Hematology
Trabzon, 61800
United Kingdom4 sites
KINGS COLLEGE HOSPITAL; Commercial R&D Amendments, Kings Health Partners Clinical Trials Office
London, SE1 9RT
Christie Hospital Nhs Trust; Medical Oncology
Manchester, M2O 4BX
Nottingham City Hospital; Dept of Haematology
Nottingham, NG5 1PB
Southampton General Hospital; Somers Cancer Research Building
Southampton, SO16 6YD
Hungary3 sites
Semmelweis University, First Dept of Medicine
Budapest, 1083
National Institute of Oncology, A Dept of Internal Medicine
Budapest, 1122
University of Debrecen Medical and Health Science Center, Institute of Internal medicine Building B
Debrecen, 4032
South Korea2 sites
Seoul National University Hospital
Seoul, 03080
Samsung Medical Center
Seoul, 06351
About this study
Official title: A Phase IB/II Study Evaluating The Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin in Combination With Rituximab (R) or Obinutuzumab (G) Plus Bendamustine (B) in Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18 weeks for participants with DLBCL and 24 weeks for participants with FL.
- Conditions
- Lymphoma
- Being tested
- Bendamustine, Obinutuzumab, Polatuzumab vedotin (Liquid), Rituximab, Polatuzumab vedotin (Lyophilized)
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendamustineDrug
Also called Treanda; Ribomustin; Levact
Bendamustine 90 milligrams per meter-squared (mg/m^2) per day administered IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).
ObinutuzumabDrug
Also called GA101; Gazyva; Gazyvaro
Obinutuzumab 1000 milligrams (mg) IV on Days 1, 8, and 15 of Cycle 1 and on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).
Polatuzumab vedotin (Liquid)Drug
Also called DCDS4501A
Polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) administered IV on Day 2 of Cycle 1, then on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).
RituximabDrug
Also called Rituxan; MabThera
Rituximab standard dose, 375 mg/m^2 IV on Day 1 of each cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL).
Polatuzumab vedotin (Lyophilized)Drug
Also called DCDS4501S
Participants in the New Formulation (NF) Cohort (Arms G and H) will follow the same schedule and dosing requirements as participants in the other Phase II cohorts (Arms A-F).
| Study group | Role | What they receive |
|---|---|---|
| Arm A (Phase II Randomization): Polatuzumab+BR in FL | Experimental | Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL. Receives: Drug: Bendamustine; Drug: Polatuzumab vedotin (Liquid); Drug: Rituximab |
| Arm B (Phase II Randomization): BR in FL | Active comparator | Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL. Receives: Drug: Bendamustine; Drug: Rituximab |
| Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL | Experimental | Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL. Receives: Drug: Bendamustine; Drug: Polatuzumab vedotin (Liquid); Drug: Rituximab |
| Arm D (Phase II Randomization): BR in DLBCL | Active comparator | Bendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL. Receives: Drug: Bendamustine; Drug: Rituximab |
| Arm E (Phase II Expansion): Polatuzumab+BG in FL | Experimental | Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL. Receives: Drug: Bendamustine; Drug: Obinutuzumab; Drug: Polatuzumab vedotin (Liquid) |
| Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL | Experimental | Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL. Receives: Drug: Bendamustine; Drug: Obinutuzumab; Drug: Polatuzumab vedotin (Liquid) |
| Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL | Experimental | Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL. Receives: Drug: Bendamustine; Drug: Polatuzumab vedotin (Liquid); Drug: Rituximab |
| Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL | Experimental | Polatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL. Receives: Drug: Bendamustine; Drug: Polatuzumab vedotin (Liquid); Drug: Rituximab |
| Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL | Experimental | Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL. Receives: Drug: Bendamustine; Drug: Obinutuzumab; Drug: Polatuzumab vedotin (Liquid) |
| Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL | Experimental | Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL. Receives: Drug: Bendamustine; Drug: Obinutuzumab; Drug: Polatuzumab vedotin (Liquid) |
| Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL | Experimental | In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL. Receives: Drug: Bendamustine; Drug: Rituximab; Drug: Polatuzumab vedotin (Lyophilized) |
| Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL | Experimental | In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL. Receives: Drug: Bendamustine; Drug: Rituximab; Drug: Polatuzumab vedotin (Lyophilized) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib: Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).
Measured: From the study start up to the end of the study (up to approximately 84 months)
Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Measured: From Month 37 to Month 84 (up to approximately 47 months)
Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin
The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Measured: Baseline up to approximately Month 24
Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Measured: Baseline up to approximately Month 24
Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)
The number of participants with positive results for ADA against lyophilized pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Measured: From Month 37 to Month 84 (up to approximately 47 months)
Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)
CR was assessed by IRC at PRA according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Measured: 6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)
Pharmacokinetic (PK) of three pola-related analytes: antibody conjugated monomethyl auristatin E (acMMAE), total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is nanograms*day per milliliters.
Measured: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is milliliters per day per kilograms (mL/day/kg)
Measured: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Secondary outcomes (67)
Phase II: Percentage of Participants With AEs
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Measured: From the study start up to the end of the study (up to approximately 84 months)
Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin
The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Measured: Baseline to approximately Month 24
Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Measured: Baseline to approximately Month 24
Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
CR was assessed by investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. Bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
CR was determined by investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 centimetres (cm) in in longest transverse diameter (LDi) and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
CR was determined by IRC a at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts). As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in sum of the products of greatest diameters (SPD) of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; bone marrow normal by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts).
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator
BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no uptake(UT) above background;2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in LN \& ELS, score=4 or 5, reduced UT than baseline (BL) \& residual mass of any size;residual UT>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Measured: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC
BOR=CR/PR per PET-CT/CT per MLRC.CR per PET-CT=complete MR in LN \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no uptake(UT) above background;2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in LN \& ELS, score=4 or 5, reduced UT than baseline (BL) \& residual mass of any size;residual UT>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Measured: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator
DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT> background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT>UT in normal bone marrow but<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Measured: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC
DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT> background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT>UT in normal bone marrow but<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Measured: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator
PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Measured: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC
PFS was defined as the time randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Measured: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
CR was assessed by Investigator at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately>liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC according to MLRC. Per MLRC, CR based on PET-CT= complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass on 5PS, where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions ; no new lesions and no evidence of FDG-avid disease in bone marrow, bone marrow normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes and ELS with a score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size at interim, residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed).
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator
BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in lymph nodes \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no UT above background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in lymph nodes \& ELS, score=4 or 5, reduced UT than BL \& residual mass of any size;residual UT>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Measured: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC
BOR=CR/PR per PET-CT/CT per MLRC. CR per PET-CT=complete MR in lymph nodes \& ELS, score=1, 2,3 with/without a residual mass on 5-PS; 1=no UT above background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT markedly higher than liver \&/or new lesions;no evidence of FDG-avid disease, bone marrow morphology=normal;if indeterminate, is IHC negative.PR per PET-CT=partial MR in lymph nodes \& ELS, score=4 or 5, reduced UT than BL \& residual mass of any size;residual UT>UT in normal marrow but reduced than BL.CR per CT=complete radiologic response with target nodes/nodal masses regressed to ≤1.5cm in LDi \& no ELS of disease, absences of non-measured lesion;organ enlargement regressed to normal;no new lesions;bone marrow= normal;if indeterminate, is IHC negative.PR per CT=≥50% decrease in SPD of up to 6 target nodes \& extranodal sites;non-measured lesions=absent/normal/regressed/no increase;spleen=regressed by ≥50% in length beyond normal, no new lesions.
Measured: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator
DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per investigator per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT> background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT>UT in normal bone marrow but<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Measured: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC
DOR=first occurrence of CR/PR to disease progression/relapse/death per PET-CT/CT, per IRC per MLRC.CR per PET-CT=score 1/2/3 with/without a residual mass on 5-PS for LN and ELS;1=no UT> background; 2=UT≤mediastinum;3=UT>mediastinum but ≤liver;4=UT moderately>liver;5=UT>than liver \&/or new lesions;bone marrow morphology=no evidence of FDG-avid disease, normal;if indeterminate IHC negative.PR per PET-CT=score of 4/5 with reduced UT compared to BL \& residual mass of any size at interim for LN \& ELS;residual UT>UT in normal bone marrow but<than BL. CR per CT=target nodes/nodal masses regressed to ≤1.5cm in LDi no ELS of disease for LN \& ELS, no non-measured lesion, organ enlargement regressed to normal; bone marrow=normal morphology; if indeterminate, IHC negative. PR per CT= ≥50% decrease SPD of 6 target measurable LN and extranodal sites, absent/normal/regressed but no increase in non-measured lesions, spleen ≥50% in length beyond normal involvement, no new sites of lesions.
Measured: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator
PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the investigators assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Measured: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC
PFS was defined as the time from randomization or from first study treatment (for obinuzumab arms) to the first occurrence of disease progression, relapse or death, from any cause based on PET-CT or CT only, as determined by the IRC assessment. As pre-specified in the protocol data reported is combined for Arms G and H.
Measured: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator
EFS was defined as time from randomization to disease progression or relapse, as assessed by the investigator or death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.
Measured: From Month 37 to Month 84 (up to approximately 47 months)
Phase II NF Cohorts: Overall Survival (OS)
OS was defined as the time from the date of randomization or first treatment (for obinutuzumab arms) to the date of death from any cause. As pre-specified in the protocol data reported is combined for Arms G and H.
Measured: From Month 37 to Month 84 (up to approximately 47 months)
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
CR was determined by Investigator at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number.
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
CR was determined by IRC at PRA according to the MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts). Values have been rounded off to the nearest whole number.
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the investigator based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
OR at PRA was defined as the percentage of participants with CR or PR at the PRA, as assessed by the IRC based on MLRC. Per MLRC, CR based on CT was defined as complete radiologic response in lymph nodes and ELS with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi and no ELS of disease organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative. PR per CT only was defined as partial remission in lymph nodes and ELS with ≥50% decrease in SPD of up to 6 target measurable lymph nodes and extranodal sites, absent/normal/regressed but with no increase in non-measured lesions, spleen regressing by ≥50% in length beyond normal it, no new sites of lesions. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts).
Measured: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
PK of pola-related analyte acMMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Measured: Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
PK of one pola-related analytes: acMMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.
Measured: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab
PK of pola-related analyte Total Ab was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Measured: Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months)
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab
PK of pola-related analyte: Total Ab was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.
Measured: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
PK of pola-related analytes unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Measured: Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
PK of one pola-related analytes: Unconjugated MMAE was measured. Cycle length is 21 days for DLBCL cohorts. As pre-specified in the protocol data is reported combined for arms G+H.
Measured: Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose
Plasma Concentration of Bendamustine
Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol plasma concentration of bendamustine was not assessed in the Phase II NF Cohort (Arm G+H).
Measured: Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose
Serum Concentration of Rituximab
Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts. As pre specified in the protocol serum concentration of rituximab was not assessed in the Phase II NF Cohort (Arm G+H).
Measured: Cycle 1 Days 1: pre-dose and 30 min post dose; Cycle 2 and 4 Day 1: pre-dose; unscheduled visits: pre-dose and 30 min post dose (up to approximately 84 months)
Serum Concentration of Obinutuzumab
Cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts.
Measured: Cycles 1 and 4 Days 1: pre-dose and 30 min post dose; Cycle 2 Day1: pre-dose; Follow up visits on Day 1: Months 3, 6, 12, 18 and 24; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase Ib: Cmax of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycles 1, 2 and 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: Cmax of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
PK of three pola-related analytes: acMMAE, total antibody and unconjugated MMAE were measured.
Measured: Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: Cmax of Bendamustine and Rituximab in Arms B and D
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: Cmax of Polatuzumab Vedotin, Obinutuzumab and Bendamustine in Arms E and F
PK of three pola-related analytes: acMMAE, unconjugated MMAE and total antibody were measured.
Measured: Cycle 1; Cycle 4 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Arm H (Phase II NF Cohort): Cmax of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Phase Ib: AUC From Time Zero to Infinity (AUCinf) of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is day*micrograms per milliliter [day*ug/mL]).
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase Ib: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Rituximab in Arms A and C
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: AUCinf of Bendamustine and Rituximab in Arms B and D
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: AUCinf of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Arms E and F
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Arm H (Phase II NF Cohort): AUC of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: antibody acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Rituximab in Cohort 1a
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase Ib: CL of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: CL of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: CL of Bendamustine and Rituximab in Arms B and D
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: CL of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Arm H (Phase II NF Cohort): CL of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1a
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase Ib: Vss of Polatuzumab Vedotin, Bendamustine, and Obinutuzumab in Cohort 1b
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Rituximab in Arms A and C
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: Vss of Bendamustine and Rituximab in Arms B and D
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Phase II: Vss of Polatuzumab Vedotin, Bendamustine and Obinutuzumab in Arms E and F
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Cycle 1 Day 2 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts)
Arm H (Phase II NF Cohort): Vss of Polatuzumab Vedotin (Lyophilized)
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Measured: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
Symptom Severity and Interference According to Therapy-Induced Neuropathy Assessment Score (TINAS) in Arms A-F
The TINAS is an 11-item questionnaire that assesses the severity of neuropathy-related symptoms in the last 24 hours. The 11 items assessed were: hot/burning sensations in hands/feet, sensations pins and needles arms/legs, numbness or tingling in hands/feet, sensations of electric shock, pain when touching cold things, cramps in hands/feet, discomfort when touching things, discomfort skin contact with something, trouble grasping small objects, trouble walking loss feeling legs/feet, difficulty balance loss feeling leg/feet. Each item was scored on a 0-10 scale, with 0 being the symptom is not present, and 10 being the symptom is as bad as the participant can imagine. Higher scores indicate more severe disease. Scores were averaged at each week.
Measured: Every week during treatment (up to 24 weeks) and for the first 2 months after treatment, thereafter every month for 10 months or until withdrawal (up to 18 months overall)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2014 (estimated)
- Study start15 Oct 2014
- Primary completion21 Oct 2021
- Study completion21 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 331 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02257567
- Sponsor's protocol ID
- GO29365
- Other IDs
- 2014-001361-28, 2014
- Status last verified
- Oct 2022
- First submitted
- 2 Oct 2014
- Last updated
- 14 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Jemaa S, Ounadjela S, Wang X, El-Galaly TC, Kostakoglu L, Knapp A, Ku G, Musick L, Sahin D, Wei MC, Yin S, Bengtsson T, De Crespigny A, Carano RAD. Automated Lugano Metabolic Response Assessment in 18F-Fluorodeoxyglucose-Avid Non-Hodgkin Lymphoma With Deep Learning on 18F-Fluorodeoxyglucose-Positron Emission Tomography. J Clin Oncol. 2024 Sep 1;42(25):2966-2977. doi: 10.1200/JCO.23.01978. Epub 2024 Jun 6.
PubMed 38843483Bosch F, Kuruvilla J, Vassilakopoulos TP, Maio DD, Wei MC, Zumofen MB, Nastoupil LJ. Indirect Treatment Comparisons of Mosunetuzumab With Third- and Later-Line Treatments for Relapsed/Refractory Follicular Lymphoma. Clin Lymphoma Myeloma Leuk. 2024 Feb;24(2):105-121. doi: 10.1016/j.clml.2023.09.007. Epub 2023 Sep 28.
PubMed 37981564Herrera AF, Tracy S, Croft B, Opat S, Ray J, Lovejoy AF, Musick L, Paulson JN, Sehn LH, Jiang Y. Risk profiling of patients with relapsed/refractory diffuse large B-cell lymphoma by measuring circulating tumor DNA. Blood Adv. 2022 Mar 22;6(6):1651-1660. doi: 10.1182/bloodadvances.2021006415.
PubMed 35086141Sehn LH, Hertzberg M, Opat S, Herrera AF, Assouline S, Flowers CR, Kim TM, McMillan A, Ozcan M, Safar V, Salles G, Ku G, Hirata J, Chang YM, Musick L, Matasar MJ. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022 Jan 25;6(2):533-543. doi: 10.1182/bloodadvances.2021005794.
PubMed 34749395Betts KA, Thuresson PO, Felizzi F, Du EX, Dieye I, Li J, Schulz M, Masaquel AS. US cost-effectiveness of polatuzumab vedotin, bendamustine and rituximab in diffuse large B-cell lymphoma. J Comp Eff Res. 2020 Oct;9(14):1003-1015. doi: 10.2217/cer-2020-0057. Epub 2020 Oct 8.
PubMed 33028076Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.
PubMed 32770353Lu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.
PubMed 32705923Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10;38(2):155-165. doi: 10.1200/JCO.19.00172. Epub 2019 Nov 6.
PubMed 31693429
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB/II Study Evaluating The Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin in Combination With Rituximab (R) or Obinutuzumab (G) Plus Bendamustine (B) in Relapsed or Refractory Follicular or Diffuse Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT02257567
- Acronym / sponsor ID
- GO29365
- Conditions
- Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 331 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 15 Oct 2014 (actual)
- Primary completion
- 21 Oct 2021 (actual)
- Study completion
- 21 Oct 2021 (actual)
- First posted
- 6 Oct 2014 (estimated)
- Results
- Posted 14 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with standard doses of bendamustine (B) and rituximab (R) or obinutuzumab (G) in participants with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). The study comprises two stages: a Phase Ib safety run-in stage and a Phase II stage. The anticipated time on treatment is 18 weeks for participants with DLBCL and 24 weeks for participants with FL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| Arm A (Phase II Randomization): Polatuzumab+BR in FL | Experimental | Drug: Bendamustine, Drug: Polatuzumab vedotin (Liquid), Drug: RituximabPolatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL. |
| Arm B (Phase II Randomization): BR in FL | Active comparator | Drug: Bendamustine, Drug: RituximabBendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with FL. |
| Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL | Experimental | Drug: Bendamustine, Drug: Polatuzumab vedotin (Liquid), Drug: RituximabPolatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL. |
| Arm D (Phase II Randomization): BR in DLBCL | Active comparator | Drug: Bendamustine, Drug: RituximabBendamustine and rituximab will be administered alone (that is, without polatuzumab vedotin) as a control arm in participants with DLBCL. |
| Arm E (Phase II Expansion): Polatuzumab+BG in FL | Experimental | Drug: Bendamustine, Drug: Obinutuzumab, Drug: Polatuzumab vedotin (Liquid)Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL. |
| Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL | Experimental | Drug: Bendamustine, Drug: Obinutuzumab, Drug: Polatuzumab vedotin (Liquid)Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL. |
| Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL | Experimental | Drug: Bendamustine, Drug: Polatuzumab vedotin (Liquid), Drug: RituximabPolatuzumab vedotin will be administered with bendamustine and rituximab in participants with DLBCL. |
| Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL | Experimental | Drug: Bendamustine, Drug: Polatuzumab vedotin (Liquid), Drug: RituximabPolatuzumab vedotin will be administered with bendamustine and rituximab in participants with FL. |
| Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL | Experimental | Drug: Bendamustine, Drug: Obinutuzumab, Drug: Polatuzumab vedotin (Liquid)Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with DLBCL. |
| Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL | Experimental | Drug: Bendamustine, Drug: Obinutuzumab, Drug: Polatuzumab vedotin (Liquid)Polatuzumab vedotin will be administered with bendamustine and obinutuzumab in participants with FL. |
| Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL | Experimental | Drug: Bendamustine, Drug: Rituximab, Drug: Polatuzumab vedotin (Lyophilized)In this New Formulation (NF) cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL. |
| Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL | Experimental | Drug: Bendamustine, Drug: Rituximab, Drug: Polatuzumab vedotin (Lyophilized)In this NF cohort, Polatuzumab vedotin (lyophilized) will be administered with bendamustine and rituximab in participants with DLBCL. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically confirmed relapsed or refractory FL (Grades 1, 2, or 3a) or relapsed or refractory DLBCL
- If the participant has received prior bendamustine, response duration must have been greater than (>) 1 year (for participants who have relapse disease after a prior regimen)
- At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 centimeters (cm) in its longest dimension
- Confirmed availability of archival or freshly collected tumor tissue
- The Phase II NF Cohorts (Arms G and H) will be required to submit tissue and pathology report for central pathology review.
Key exclusion criteria (20 listed)
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (MAbs, or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
- Contraindication to bendamustine, rituximab, or obinutuzumab
- Prior use of any MAb, radioimmunoconjugate, or antibody-drug conjugate (ADC) within 4 weeks or 5 half-lives before Cycle 1 Day 1
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1 Day 1
- Ongoing corticosteroid use >30 mg per day prednisone or equivalent, for purposes other than lymphoma symptom control
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BendamustineAlso: Treanda; Ribomustin; LevactBendamustine 90 milligrams per meter-squared (mg/m^2) per day administered IV on Days 2 and 3 of Cycle 1, then on Days 1 and 2 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL). | Drug | Arm A (Phase II Randomization): Polatuzumab+BR in FL, Arm B (Phase II Randomization): BR in FL, Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL, Arm D (Phase II Randomization): BR in DLBCL, Arm E (Phase II Expansion): Polatuzumab+BG in FL, Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL, Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL, Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL, Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL, Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL, Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL, Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL |
| ObinutuzumabAlso: GA101; Gazyva; GazyvaroObinutuzumab 1000 milligrams (mg) IV on Days 1, 8, and 15 of Cycle 1 and on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL). | Drug | Arm E (Phase II Expansion): Polatuzumab+BG in FL, Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL, Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL, Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL |
| Polatuzumab vedotin (Liquid)Also: DCDS4501APolatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) administered IV on Day 2 of Cycle 1, then on Day 1 of each subsequent cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL). | Drug | Arm A (Phase II Randomization): Polatuzumab+BR in FL, Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL, Arm E (Phase II Expansion): Polatuzumab+BG in FL, Arm F (Phase II Expansion): Polatuzumab+BG in DLBCL, Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL, Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL, Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in DLBCL, Cohort 1B (Phase Ib Safety Run-In): Polatuzumab+BG in FL |
| RituximabAlso: Rituxan; MabTheraRituximab standard dose, 375 mg/m^2 IV on Day 1 of each cycle for up to 6 cycles (each cycle is 21 days in DLBCL and 28 days in FL). | Drug | Arm A (Phase II Randomization): Polatuzumab+BR in FL, Arm B (Phase II Randomization): BR in FL, Arm C (Phase II Randomization): Polatuzumab+BR in DLBCL, Arm D (Phase II Randomization): BR in DLBCL, Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL, Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL, Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in DLBCL, Cohort 1A (Phase Ib Safety Run-In): Polatuzumab+BR in FL |
| Polatuzumab vedotin (Lyophilized)Also: DCDS4501SParticipants in the New Formulation (NF) Cohort (Arms G and H) will follow the same schedule and dosing requirements as participants in the other Phase II cohorts (Arms A-F). | Drug | Arm G (Phase II NF Cohort): Polatuzumab+BR in DLBCL, Arm H (Phase II NF Cohort): Polatuzumab+BR in DLBCL |
Primary outcome
Phase Ib: Percentage of Participants With Adverse Events (AEs)
Time frame: From the study start up to the end of the study (up to approximately 84 months)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0).
Arm G+H (Phase II NF Cohort): Percentage of Participants With AEs
Time frame: From Month 37 to Month 84 (up to approximately 47 months)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. AEs were reported based on the NCI-CTCAE, v4.0. As pre-specified in the protocol data reported is combined for Arms G and H. Values have been rounded off to the nearest whole number.
Cohort 1a (Phase Ib): Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs) to Polatuzumab Vedotin
Time frame: Baseline up to approximately Month 24
The number of participants with positive results for ADA against pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 titer unit (t.u.) greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Cohort 1b (Phase Ib): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
Time frame: Baseline up to approximately Month 24
The number of participants with positive results for ADA against pola and obinutuzumab at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Arms G+H: (Phase II NF Cohorts): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin (Lyophilized)
Time frame: From Month 37 to Month 84 (up to approximately 47 months)
The number of participants with positive results for ADA against lyophilized pola at Baseline and at any of the post-baseline assessment time-points were reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at baseline who has one or more post-baseline titer results that are at least 0.60 t.u. greater than the baseline titer result. Treatment emergent ADA is the sum of treatment-induced ADAs and treatment enhanced ADAs. Values have been rounded off to the nearest whole number.
Phase II Randomized and NF Cohorts: Percentage of Participants With Complete Response (CR) at Primary Response Assessment (PRA) Based on Positron Emission Tomography (PET)-Computed Tomography (CT) Scan as Determined by Independent Review Committee (IRC)
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
CR was assessed by IRC at PRA according to Modified Lugano Response Criteria (MLRC). Per MLRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites (ELS) with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS) where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, immunohistochemistry (IHC) negative. As pre-specified in the protocol data reported is combined for Arms G and H. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts and 28 days for FL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Arm H (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
Time frame: 6-8 weeks after Cycle 6, Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
CR was assessed by IRC at PRA according to MLRC. Per MLRC, CR based on PET-CT was defined as complete MR in lymph nodes and ELS with a score of 1, 2, or 3 with or without residual mass, on 5PS where 1=no uptake above background; 2=uptake ≤ mediastinum; 3=uptake > mediastinum but ≤ liver; 4=uptake moderately > liver; 5=uptake markedly higher than liver and/or new lesions no evidence of FDG-avid disease in bone marrow. Bone marrow is normal by morphology; if indeterminate, IHC negative. The analysis was done 6-8 weeks after Cycle 6, Day 1 (each cycle is 21 days for DLBCL cohorts) or after final dose of study treatment. Values have been rounded off to the nearest whole number.
Arm G (Phase II NF Cohort): Area Under Concentration-Time Curve (AUC) of Polatuzumab Vedotin (Lyophilized)
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (each cycle is 21 days DLBCL cohorts) up to approximately 9 weeks
Pharmacokinetic (PK) of three pola-related analytes: antibody conjugated monomethyl auristatin E (acMMAE), total antibody, and unconjugated MMAE were measured. The unit of measure for AUC is nanograms*day per milliliters.
Arm G (Phase II NF Cohort): Maximum Concentration (Cmax) of Polatuzumab Vedotin (Lyophilized)
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4,(cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
Arm G (Phase II NF Cohort): Systemic Clearance (CL) of Polatuzumab Vedotin (Lyophilized)
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured. Unit of measure for CL is milliliters per day per kilograms (mL/day/kg)
Arm G (Phase II NF Cohort): Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin (Lyophilized)
Time frame: Days 2, 8 and 15 of Cycle 1, Day 1 of Cycle 2 and 4, Day (cycle length is 21 days for DLBCL cohorts) up to approximately 9 weeks
PK of three pola-related analytes: acMMAE, total antibody, and unconjugated MMAE were measured.
67 secondary outcomes
Phase II: Percentage of Participants With AEs
Time frame: From the study start up to the end of the study (up to approximately 84 months)
Arms A and C (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin
Time frame: Baseline to approximately Month 24
Arms E and F (Phase II): Percentage of Participants With Treatment Emergent ADAs to Polatuzumab Vedotin and Obinutuzumab
Time frame: Baseline to approximately Month 24
Phase II: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II Expansion Cohorts and Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With Objective Response (OR) at PRA Based on PET-CT as Determined by Investigator
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts and 28 days for FL cohorts) or last dose of study drug (up to approximately 28 weeks)
Phase II: Percentage of Participants With Best Objective Response (BOR) Based on PET-CT or CT Only as Determined by the Investigator
Time frame: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
DLBCL Cohorts: Percentage of Participants With BOR Based PET-CT or CT Only as Determined by IRC
Time frame: Up to every 6 months until disease progression, withdrawal or study completion (up to approximately 84 months)
DLBCL Cohorts: Duration of Response (DOR) Based on PET-CT or CT Only as Determined by the Investigator
Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
DLBCL Cohorts: DOR Based on PET-CT or CT Only as Determined by the IRC
Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (up to approximately 84 months)
DLBCL Cohorts: Progression Free Survival (PFS) Based on PET-CT or CT Only as Determined by the Investigator
Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
DLBCL Cohorts: PFS Based on PET-CT or CT Only as Determined by the IRC
Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (up to approximately 84 months)
Phase II NF Cohort: Percentage of Participants With CR at PRA Based on PET-CT as Determined by the Investigator
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by Investigator
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Phase II NF Cohort: Percentage of Participants With OR at PRA Based on PET-CT as Determined by IRC
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the Investigator
Time frame: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohorts: Percentage of Participants With BOR Based on PET-CT or CT Only as Determined by the IRC
Time frame: Up to every 6 months until disease progression, withdrawal or study completion (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the Investigator
Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: DOR Based on PET-CT or CT Only as Determined by the IRC
Time frame: From the date of the first occurrence of a documented CR or PR to the date of disease progression, relapse, or death from any cause whichever occur first (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the Investigator
Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: PFS Based on PET-CT or CT Only as Determined by the IRC
Time frame: From the date of randomization or first treatment to the first occurrence of progression or relapse, or death from any cause (from Month 37 to Month 84 [up to approximately 47 months])
Phase II NF Cohort: Event-Free Survival (EFS) Based on PET-CT or CT Only, as Determined by the Investigator
Time frame: From Month 37 to Month 84 (up to approximately 47 months)
Phase II NF Cohorts: Overall Survival (OS)
Time frame: From Month 37 to Month 84 (up to approximately 47 months)
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on PET-CT as Determined by the IRC
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by Investigator
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Arm G (Phase II NF Cohort): Percentage of Participants With CR at PRA Based on CT Only as Determined by IRC
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to approximately 23 weeks)
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by Investigator
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
Arm G (Phase II NF Cohort): Percentage of Participants With OR at PRA Based on CT Only as Determined by IRC
Time frame: 6 to 8 weeks after Cycle 6 Day 1 (cycle length is 21 days for DLBCL cohorts) or last dose of study drug (up to 23 weeks)
Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
Time frame: Cycle 1 Day 2: pre-dose and 30 minutes (min) post dose; Cycle 1 Days 8 and 15; Cycle 2 and 4 Day 1: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Arm G+H (Phase II NF Cohorts): Plasma Concentration of of Polatuzumab Vedotin Analyte: acMMAE
Time frame: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
Serum Concentration of of Polatuzumab Vedotin Analyte: Total Ab
Time frame: Cycle 1 Days 2: pre-dose & 30 min post dose; Cycle 1 Days 8 & 15; Cycle 2 and 4 Day 1 and unscheduled visits: pre-dose & 30 min post dose; Follow up at Day 1: Months 3, 6, 12, 18 & 24; study treatment completion visit (up to approx. 84 months)
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Total Ab
Time frame: Cycle 1 Day 2: post dose; Cycle 2 and 4 Day 1: pre-dose and post dose
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
Time frame: Cycle 1 Day 2: pre-dose and 30 min post dose, Cycle 1 Days 8 and 15; Cycles 2 and 4: pre-dose and 30 min post dose; unscheduled visits: pre-dose and 30 min post dose; study treatment completion (up to approximately 84 months)
Arm G+H (Phase II NF Cohorts): Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
Time frame: Cycle 1 Day 2: post dose; Cycle 1 and 3 Day 8 and 15; Cycle 2, 3 and 4 Day 1: pre-dose and post dose
Plasma Concentration of Bendamustine
Time frame: Cycle 1 Day 2: pre-dose, 5 min, 1 hour (h); 2h, 3h and 4h post dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38843483Jemaa S, Ounadjela S, Wang X, El-Galaly TC, Kostakoglu L, Knapp A, Ku G, Musick L, Sahin D, Wei MC, Yin S, Bengtsson T, De Crespigny A, Carano RAD. Automated Lugano Metabolic Response Assessment in 18F-Fluorodeoxyglucose-Avid Non-Hodgkin Lymphoma With Deep Learning on 18F-Fluorodeoxyglucose-Positron Emission Tomography. J Clin Oncol. 2024 Sep 1;42(25):2966-2977. doi: 10.1200/JCO.23.01978. Epub 2024 Jun 6.
- Derived from this study: PubMed 37981564Bosch F, Kuruvilla J, Vassilakopoulos TP, Maio DD, Wei MC, Zumofen MB, Nastoupil LJ. Indirect Treatment Comparisons of Mosunetuzumab With Third- and Later-Line Treatments for Relapsed/Refractory Follicular Lymphoma. Clin Lymphoma Myeloma Leuk. 2024 Feb;24(2):105-121. doi: 10.1016/j.clml.2023.09.007. Epub 2023 Sep 28.
- Derived from this study: PubMed 35086141Herrera AF, Tracy S, Croft B, Opat S, Ray J, Lovejoy AF, Musick L, Paulson JN, Sehn LH, Jiang Y. Risk profiling of patients with relapsed/refractory diffuse large B-cell lymphoma by measuring circulating tumor DNA. Blood Adv. 2022 Mar 22;6(6):1651-1660. doi: 10.1182/bloodadvances.2021006415.
- Derived from this study: PubMed 34749395Sehn LH, Hertzberg M, Opat S, Herrera AF, Assouline S, Flowers CR, Kim TM, McMillan A, Ozcan M, Safar V, Salles G, Ku G, Hirata J, Chang YM, Musick L, Matasar MJ. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022 Jan 25;6(2):533-543. doi: 10.1182/bloodadvances.2021005794.
- Derived from this study: PubMed 33028076Betts KA, Thuresson PO, Felizzi F, Du EX, Dieye I, Li J, Schulz M, Masaquel AS. US cost-effectiveness of polatuzumab vedotin, bendamustine and rituximab in diffuse large B-cell lymphoma. J Comp Eff Res. 2020 Oct;9(14):1003-1015. doi: 10.2217/cer-2020-0057. Epub 2020 Oct 8.
- Derived from this study: PubMed 32770353Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.
- Derived from this study: PubMed 32705923Lu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.
- Derived from this study: PubMed 31693429Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10;38(2):155-165. doi: 10.1200/JCO.19.00172. Epub 2019 Nov 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
62 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bendamustine, Obinutuzumab and Polatuzumab vedotin (Liquid) in people with Lymphoma, run by Hoffmann-La Roche at 62 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 62 sites in United States, France, Germany, Spain, Australia and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: Percentage of Participants With Adverse Events (AEs) (time frame: From the study start up to the end of the study (up to approximately 84 months)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02257567, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2022.