Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell LymphomaPhase 1/2NCT02600897
A Study of Obinutuzumab, Polatuzumab Vedotin, and Lenalidomide in Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
A Phase 1/2 study testing Lenalidomide, Obinutuzumab and Polatuzumab Vedotin in people with Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma, run by Hoffmann-La Roche at 28 sites in 3 countries.
Trial summary
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and lenalidomide in participants with relapsed or refractory (R/R) follicular lymphoma (FL) and rituximab in combination with polatuzumab vedotin and lenalidomide in participants with R/R… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- What is being tested?
- Lenalidomide, Obinutuzumab and Polatuzumab Vedotin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 28 sitesin 3 countries
- Study dates
- 24 Mar 2016to 15 Dec 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
- Age greater than or equal to (>/=) 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- For obinutuzumab in combination with polatuzumab vedotin and lenalidomide (G + Pola + Len) treatment group: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
- For rituximab in combination with polatuzumab vedotin and lenalidomide (R + Pola + Len) treatment group: R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in patients who are not eligible for autologous stem-cell transplantation or who have experienced disease progression following treatment with high-dose chemotherapy plus autologous stem-cell transplantation
- Histologically documented CD20-positive B-cell lymphoma as determined by the local laboratory
- fluorodeoxyglucose (FDG)-avid lymphoma (i.e., positron emission tomography (PET)-positive lymphoma)
- At least one bi-dimensionally measurable lesion
- Agreement to remain abstinent or use adequate contraception, among women or men of childbearing potential
Who cannot join
- Grade 3b follicular lymphoma
- History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
- Known CD20-negative status at relapse or progression
- Central nervous system (CNS) lymphoma or leptomeningeal infiltration
- Prior allogeneic stem-cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
- Current use of systemic immunosuppressant(s), or prior anti-cancer therapy to include: lenalidomide, fludarabine, or alemtuzumab within 12 months; radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
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- Active infection
- Positive for human immunodeficiency virus (HIV) or hepatitis B or C
- Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1
- Poor hematologic, renal, or hepatic function
- Pregnant or lactating women
- Life expectancy less than (<) 3 months
Trial locations and contacts
28 sites in 3 countries.
28 sites in 3 countries
Spain11 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clínic. Barcelona
Barcelona, 08036
Hospital Santa Creu i Sant Pau
Barcelona, 08041
Insititut Catala D'Oncologia
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital Gregorio Marañon
Madrid, 28007
H. Universitario Leonor
Madrid, 28031
Hospital Universitario Fundacion Jimenez Diaz.
Madrid, 28040
Hospital Clínico Málaga
Málaga, Malaga, 29010
Complejo Hospitalario de Navarra
Pamplona, Navarre, 31008
Clínica Universidad de Navarra
Pamplona, Navarre, 31620
Hospital La Fe
Valencia
United Kingdom9 sites
St James University Hospital
Leeds, LS9 7TF
University Hospitals of Leicester NHS Trust - Leicester Royal Infirmary
Leicester, LE1 5WW
Royal Liverpool University Hospital
Liverpool, L7 8XP
Barts Hospital; Institute of Cancer
London, EC1M 6BQ
Sarah Cannon Research Institute
London, W1G 6AD
Maidstone & Tonbridge Wells Hospital; Kent Oncology Center
Maidstone, ME16 9QQ
Nottingham University Hospitals NHS Trust - City Hospital
Nottingham, NG5 1PB
Barking, Havering and Redbridge University Hospitals NHS Trust - Queen's Hospital
Romford, RM7 0AG
The Royal Wolverhampton Hospitals NHS Trust; Department of Haematology
Wolverhampton, WV10 0QP
United States8 sites
University of Missouri/Ellis Fischel
Columbia, Missouri, 65212
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
Rocky Mountain Cancer Centers, LLP
Irving, Texas, 75063
Texas Oncology-Tyler
Irving, Texas, 75063
Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital
Marietta, Georgia, 30060
NYU School of Medicine
New York, New York, 10016
Texas Oncology San Antonio Medical Center
San Antonio, Texas, 78240
Washington University; Wash Uni. Sch. Of Med
St Louis, Missouri, 63110
About this study
Official title: A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and lenalidomide in participants with relapsed or refractory (R/R) follicular lymphoma (FL) and rituximab in combination with polatuzumab vedotin and lenalidomide in participants with R/R diffuse large B-cell lymphoma (DLBCL), followed by post-induction treatment with obinutuzumab in combination with lenalidomide in participants with FL who achieve a complete response (CR), partial response (PR), or stable disease (SD) at end of induction (EOI) and post-induction treatment with rituximab plus lenalidomide in participants with DLBCL who achieve a CR or PR at EOI.
- Conditions
- Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- Being tested
- Lenalidomide, Obinutuzumab, Polatuzumab Vedotin, Rituximab
- Medical subject headings
- Recurrence, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
All participants will receive lenalidomide oral capsules at doses of 10, 15, or 20 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by post-induction treatment at a dose of 10 mg once daily on Days 1 to 21 of each subsequent 28-day cycle. Post-induction lenalidomide may continue for up to 12 months until disease progression or unacceptable toxicity for participants with R/R FL and up to 6 months until disease progression or unacceptable toxicity for participants with R/R DLBCL.
ObinutuzumabDrug
Participants will receive a fixed dose of obinutuzumab, 1000 mg via intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 followed by post-induction treatment at a dose of 1000 mg via IV infusion on Day 1 of every other month for up to 24 months until disease progression or unacceptable toxicity.
Polatuzumab VedotinDrug
Participants with R/R FL will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) on Day 1 of each 28-day cycle for up to 6 months during induction treatment. Participants wit R/R DLBCL will receive polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 months during induction treatment.
RituximabDrug
Participants will receive a fixed dose of rituximab, 375 mg/m^2 via intravenous (IV) infusion to be given on Days 1 of Cycle 1 to 6 followed by post-induction treatment at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month for up to 6 months, until disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Dose-escalation Cohort: FL | Experimental | Participants with R/R FL will receive 6 months of induction treatment with polatuzumab vedotin and lenalidomide at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and lenalidomide when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 24-month maintenance regimen consisting of lenalidomide and obinutuzumab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle). Receives: Drug: Lenalidomide; Drug: Obinutuzumab; Drug: Polatuzumab Vedotin |
| Dose-escalation Cohort: DLBCL | Experimental | Participants with R/R DLBCL will receive 6 months of induction treatment with fixed dose of polatuzumab vedotin and rituximab along with dose escalating lenalidomide. Lenalidomide will be administered at escalating doses to identify the recommended Phase 2 dose (RP2D) for lenalidomide. Those who achieve CR and PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 6-month consolidation regimen consisting of lenalidomide and rituximab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle). Receives: Drug: Lenalidomide; Drug: Polatuzumab Vedotin; Drug: Rituximab |
| Expansion Cohort: FL | Experimental | Participants with R/R FL who received induction treatment with polatuzumab vedotin and lenalidomide, in addition to obinutuzumab and achieved CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 24-months maintenance regimen consisting of lenalidomide and obinutuzumab for first 12 months followed by obinutuzumab treatment for next 12 months. Post-induction therapy will start 8 weeks after Cycle 6 Day 1. Receives: Drug: Lenalidomide; Drug: Obinutuzumab |
| Expansion Cohort: DLBCL | Experimental | Participants with R/R DLBCL who received induction treatment with polatuzumab vedotin and lenalidomide in addition to rituximab and achieved CR or PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 6-month consolidation regimen consisting of lenalidomide and rituximab. Post-induction therapy will start 8 weeks after Cycle 6 Day 1. Receives: Drug: Lenalidomide; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
A DLT was defined as any one of the following toxicities occurring during the first cycle of treatment and assessed by the investigator as related to study treatment: Any adverse event of any grade that lead to a delay of > 14 days in the start of the next treatment cycle, Grade 3 or 4 non-hematologic adverse events with few exceptions; increase in hepatic transaminase > 3 x baseline and an increase in direct bilirubin > 2 x upper limits of normal (ULN), without any findings of cholestasis or jaundice, or signs of hepatic dysfunction, and in the absence of other contributory factors; hematologic adverse events that met a few protocol specified criteria. DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Percentages have been rounded off to the first decimal point.
Measured: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase
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. Percentages have been rounded off to the first decimal point.
Measured: From study start up to end of study (Up to a maximum of 69 months)
Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans
CR at EOI was assessed by IRC 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Measured: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Secondary outcomes (17)
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans
CR at EOI was assessed by Investigator 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Measured: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone
CR at EOI was determined by IRC 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 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Measured: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone
CR at EOI was determined by Investigator 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Measured: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans
OR was defined as percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes \& ELS with 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 \& no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. Partial response (PR) based on PET-CT was defined as partial MR in lymph nodes \& ELS with score of 4 or 5 with reduced uptake compared with baseline \& residual masses 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). Percentages have been rounded off up to the second decimal point.
Measured: 6 to 8 weeks after Day 1 of Cycle 6 (cycle=28 days) (up to approximately 28 weeks)
Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans
OR was defined percentage of participants with CR or PR assessed by the investigator according to MLRC. Per MLRC CR based on PET-CT is complete MR in lymph nodes \& ELS with score of 1, 2, 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 \& no evidence of FDG-avid disease in bone marrow.Bone marrow is normal by morphology; if indeterminate, IHC negative. PR based on PET-CT was defined as partial MR in lymph nodes \& ELS with score of 4 or 5 with reduced uptake compared with baseline \& residual masses 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). Percentages are rounded off.
Measured: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone
OR was defined as the percentage of participants with CR or PR, 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 in the 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 28 days). Percentages have been rounded off to the first decimal point.
Measured: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone
OR was defined as the percentage of participants with CR or PR, 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 the 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
Measured: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
BOR=CR/PR per CT per MLRC. Per MLRC, CR based on CT was defined as a 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 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. Percentages have been rounded off to the first decimal point.
Measured: Up to every 6 months until disease progression, unacceptable toxicity or study completion (up to approximately 69 months)
Observed Serum Obinutuzumab Concentration
1 cycle = 28 days
Measured: Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
Observed Serum Rituximab Concentration
Measured: Day 1 of Cycles 1, 2, 4, 6: predose and 30 mins post-dose (1 cycle = 28 days) (up to approximately 69 months)
Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody
Measured: Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)
Measured: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
Measured: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
Observed Plasma Lenalidomide Concentration
Measured: Day 1 Cycle 1: predose and 2 hours (hr) post-dose; Day 15 Cycle 1: predose, 0.5hr, 1hr, 2hr, 4hr, 8hr post-dose; Day 1 Cycle 6: 2hr post-dose; unscheduled visits: 2hr post-dose (1 cycle = 28 days) (up to approximately 69 months)
Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab
The number of participants with positive results for HAHAs, also called anti-drug antibodies (ADAs) against obinutuzumab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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.
Measured: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab
The number of participants with positive results for HACAs, also called ADAs against rituximab at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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.
Measured: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin
The number of participants with positive results for ATAs, also called ADAs against polatuzumab vedotin at baseline and at any of the post-baseline assessment time-points were reported. Number of participants positive for Treatment Emergent ADA = the number of post-baseline evaluable participants determined to have treatment induced ADA 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.
Measured: Baseline up to approx. 2 years after the last dose of polatuzumab vedotin (up to approximately 30 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2015 (estimated)
- Study start24 Mar 2016
- Primary completion15 Dec 2021
- Study completion15 Dec 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 (2)Papers the sponsor has linked to this study.
- Other trials for Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 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
- NCT02600897
- Sponsor's protocol ID
- GO29834
- Other IDs
- 2015-001999-22, 2015
- Status last verified
- Dec 2023
- First submitted
- 3 Nov 2015
- Last updated
- 26 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Abrisqueta P, Gonzalez-Barca E, Panizo C, Perez JMA, Miall F, Bastos-Oreiro M, Triguero A, Banerjee L, McMillan A, Seymour E, Hirata J, de Guzman J, Sharma S, Jin HY, Musick L, Diefenbach C. Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Lancet Haematol. 2024 Feb;11(2):e136-e146. doi: 10.1016/S2352-3026(23)00345-9. Epub 2024 Jan 5.
PubMed 38190832Diefenbach C, Kahl BS, McMillan A, Briones J, Banerjee L, Cordoba R, Miall F, Burke JM, Hirata J, Jiang Y, Paulson JN, Chang YM, Musick L, Abrisqueta P. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Lancet Haematol. 2021 Dec;8(12):e891-e901. doi: 10.1016/S2352-3026(21)00311-2.
PubMed 34826412
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT02600897
- Acronym / sponsor ID
- GO29834
- Conditions
- Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 24 Mar 2016 (actual)
- Primary completion
- 15 Dec 2021 (actual)
- Study completion
- 15 Dec 2021 (actual)
- First posted
- 9 Nov 2015 (estimated)
- Results
- Posted 26 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and lenalidomide in participants with relapsed or refractory (R/R) follicular lymphoma (FL) and rituximab in combination with polatuzumab vedotin and lenalidomide in participants with R/R diffuse large B-cell lymphoma (DLBCL), followed by post-induction treatment with obinutuzumab in combination with lenalidomide in participants with FL who achieve a complete response (CR), partial response (PR), or stable disease (SD) at end of induction (EOI) and post-induction treatment with rituximab plus lenalidomide in participants with DLBCL who achieve a CR or PR at EOI.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose-escalation Cohort: FL | Experimental | Drug: Lenalidomide, Drug: Obinutuzumab, Drug: Polatuzumab VedotinParticipants with R/R FL will receive 6 months of induction treatment with polatuzumab vedotin and lenalidomide at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and lenalidomide when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 24-month maintenance regimen consisting of lenalidomide and obinutuzumab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle). |
| Dose-escalation Cohort: DLBCL | Experimental | Drug: Lenalidomide, Drug: Polatuzumab Vedotin, Drug: RituximabParticipants with R/R DLBCL will receive 6 months of induction treatment with fixed dose of polatuzumab vedotin and rituximab along with dose escalating lenalidomide. Lenalidomide will be administered at escalating doses to identify the recommended Phase 2 dose (RP2D) for lenalidomide. Those who achieve CR and PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will be eligible to receive a 6-month consolidation regimen consisting of lenalidomide and rituximab, to be initiated 8 weeks after Day 1 of Cycle 6 (induction cycle). |
| Expansion Cohort: FL | Experimental | Drug: Lenalidomide, Drug: ObinutuzumabParticipants with R/R FL who received induction treatment with polatuzumab vedotin and lenalidomide, in addition to obinutuzumab and achieved CR, PR, or SD at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 24-months maintenance regimen consisting of lenalidomide and obinutuzumab for first 12 months followed by obinutuzumab treatment for next 12 months. Post-induction therapy will start 8 weeks after Cycle 6 Day 1. |
| Expansion Cohort: DLBCL | Experimental | Drug: Lenalidomide, Drug: RituximabParticipants with R/R DLBCL who received induction treatment with polatuzumab vedotin and lenalidomide in addition to rituximab and achieved CR or PR at the EOI (6-8 weeks after Day 1 of Cycle 6) will receive a 6-month consolidation regimen consisting of lenalidomide and rituximab. Post-induction therapy will start 8 weeks after Cycle 6 Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age greater than or equal to (>/=) 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- For obinutuzumab in combination with polatuzumab vedotin and lenalidomide (G + Pola + Len) treatment group: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
- For rituximab in combination with polatuzumab vedotin and lenalidomide (R + Pola + Len) treatment group: R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in patients who are not eligible for autologous stem-cell transplantation or who have experienced disease progression following treatment with high-dose chemotherapy plus autologous stem-cell transplantation
- Histologically documented CD20-positive B-cell lymphoma as determined by the local laboratory
Key exclusion criteria (12 listed)
- Grade 3b follicular lymphoma
- History of transformation of indolent disease to diffuse large B-cell lymphoma (DLBCL)
- Known CD20-negative status at relapse or progression
- Central nervous system (CNS) lymphoma or leptomeningeal infiltration
- Prior allogeneic stem-cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
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 |
|---|---|---|
| LenalidomideAll participants will receive lenalidomide oral capsules at doses of 10, 15, or 20 milligrams (mg) on Days 1 to 21 of each 28-day cycle for up to 6 Cycles in dose escalation phase followed by post-induction treatment at a dose of 10 mg once daily on Days 1 to 21 of each subsequent 28-day cycle. Post-induction lenalidomide may continue for up to 12 months until disease progression or unacceptable toxicity for participants with R/R FL and up to 6 months until disease progression or unacceptable toxicity for participants with R/R DLBCL. | Drug | Dose-escalation Cohort: DLBCL, Dose-escalation Cohort: FL, Expansion Cohort: DLBCL, Expansion Cohort: FL |
| ObinutuzumabParticipants will receive a fixed dose of obinutuzumab, 1000 mg via intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 followed by post-induction treatment at a dose of 1000 mg via IV infusion on Day 1 of every other month for up to 24 months until disease progression or unacceptable toxicity. | Drug | Dose-escalation Cohort: FL, Expansion Cohort: FL |
| Polatuzumab VedotinParticipants with R/R FL will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) on Day 1 of each 28-day cycle for up to 6 months during induction treatment. Participants wit R/R DLBCL will receive polatuzumab vedotin via IV infusion at dose 1.8 mg/kg on Day 1 of each 28-day cycle for up to 6 months during induction treatment. | Drug | Dose-escalation Cohort: DLBCL, Dose-escalation Cohort: FL |
| RituximabParticipants will receive a fixed dose of rituximab, 375 mg/m^2 via intravenous (IV) infusion to be given on Days 1 of Cycle 1 to 6 followed by post-induction treatment at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month for up to 6 months, until disease progression or unacceptable toxicity. | Drug | Dose-escalation Cohort: DLBCL, Expansion Cohort: DLBCL |
Primary outcome
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase
A DLT was defined as any one of the following toxicities occurring during the first cycle of treatment and assessed by the investigator as related to study treatment: Any adverse event of any grade that lead to a delay of > 14 days in the start of the next treatment cycle, Grade 3 or 4 non-hematologic adverse events with few exceptions; increase in hepatic transaminase > 3 x baseline and an increase in direct bilirubin > 2 x upper limits of normal (ULN), without any findings of cholestasis or jaundice, or signs of hepatic dysfunction, and in the absence of other contributory factors; hematologic adverse events that met a few protocol specified criteria. DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0). Percentages have been rounded off to the first decimal point.
Percentage of Participants With Adverse Events (AEs)
Time frame: From study start up to end of study (Up to a maximum of 69 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. Percentages have been rounded off to the first decimal point.
Percentage of Participants With Complete Response (CR) at End of Induction (EOI), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
CR at EOI was assessed by IRC 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. Analysis was done 6-8 weeks after Cycle 6, Day 1 (cycle=28 days). Percentages have been rounded off to the first decimal point.
17 secondary outcomes
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With CR at EOI, Determined by Investigator on the Basis of CT Scans Alone
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With Objective Response (OR) at EOI, Determined by the IRC on the Basis of PET-CT Scans
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (cycle=28 days) (up to approximately 28 weeks)
Percentage of Participants With Objective Response at EOI, Determined by Investigator on the Basis of PET-CT Scans
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With Objective Response at EOI, Determined by the IRC on the Basis of CT Scans Alone
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of CT Scans Alone
Time frame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks)
Percentage of Participants With Best Response of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
Time frame: Up to every 6 months until disease progression, unacceptable toxicity or study completion (up to approximately 69 months)
Observed Serum Obinutuzumab Concentration
Time frame: Day 1 of Cycles 1, 2, 4 & 6: predose & 30 mins postdose; EOI: predose; Day 1 of Maintenance Months 1,7, 13, 19;Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
Observed Serum Rituximab Concentration
Time frame: Day 1 of Cycles 1, 2, 4, 6: predose and 30 mins post-dose (1 cycle = 28 days) (up to approximately 69 months)
Serum Concentration of Polatuzumab Vedotin Analyte: Total Antibody
Time frame: Day 1 of Cycles 1, 2, 4: predose (1 cycle = 28 days), Day 120 post last dose; one year post last dose; study drug discontinuation; unscheduled visit: predose (up to approximately 69 months)
Plasma Concentration of Polatuzumab Vedotin Analyte: Antibody-conjugated MMAE (acMMAE)
Time frame: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1; Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
Plasma Concentration of Polatuzumab Vedotin Analyte: Unconjugated MMAE
Time frame: Day 1 of Cycles 1, 2, 4: predose and 30 mins post-dose; Days 8 and 15 of Cycle 1 and Day 1 of Cycle 6: predose, study drug discontinuation; unscheduled visit: predose (1 cycle = 28 days) (up to approximately 69 months)
Observed Plasma Lenalidomide Concentration
Time frame: Day 1 Cycle 1: predose and 2 hours (hr) post-dose; Day 15 Cycle 1: predose, 0.5hr, 1hr, 2hr, 4hr, 8hr post-dose; Day 1 Cycle 6: 2hr post-dose; unscheduled visits: 2hr post-dose (1 cycle = 28 days) (up to approximately 69 months)
Number of Participants With Human Anti-human Antibodies (HAHAs) to Obinutuzumab
Time frame: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
Number of Participants With Human Anti-chimeric Antibodies (HACAs) to Rituximab
Time frame: Baseline up to approximately 2 years after last dose (up to approximately 69 months)
Number of Participants With Anti-therapeutic Antibodies (ATAs) to Polatuzumab Vedotin
Time frame: Baseline up to approx. 2 years after the last dose of polatuzumab vedotin (up to approximately 30 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38190832Abrisqueta P, Gonzalez-Barca E, Panizo C, Perez JMA, Miall F, Bastos-Oreiro M, Triguero A, Banerjee L, McMillan A, Seymour E, Hirata J, de Guzman J, Sharma S, Jin HY, Musick L, Diefenbach C. Polatuzumab vedotin plus rituximab and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Lancet Haematol. 2024 Feb;11(2):e136-e146. doi: 10.1016/S2352-3026(23)00345-9. Epub 2024 Jan 5.
- Derived from this study: PubMed 34826412Diefenbach C, Kahl BS, McMillan A, Briones J, Banerjee L, Cordoba R, Miall F, Burke JM, Hirata J, Jiang Y, Paulson JN, Chang YM, Musick L, Abrisqueta P. Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Lancet Haematol. 2021 Dec;8(12):e891-e901. doi: 10.1016/S2352-3026(21)00311-2.
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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
28 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lenalidomide, Obinutuzumab and Polatuzumab Vedotin in people with Relapsed or Refractory Follicular Lymphoma, Relapsed or Refractory Diffuse Large B-Cell Lymphoma, run by Hoffmann-La Roche at 28 sites in 3 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 12 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 26 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Spain, United Kingdom, United States. 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 26 Dec 2023). 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?
Percentage of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle = 28 days) in dose-escalation phase). The study lists 3 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 NCT02600897, which also lists 2 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 26 Dec 2023.