Diffuse Large B-Cell Lymphoma, Lymphoma FollicularPhase 1/2NCT02596971
A Study of Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus (+) Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Participants With Follicular Lymphoma (FL) or Rituximab + CHOP in Participants With Diffuse Large B-Cell Lymphoma (DLBCL)
A Phase 1/2 study testing Atezolizumab, Bendamustine and Cyclophosphamide in people with Diffuse Large B-Cell Lymphoma, Lymphoma Follicular, run by Hoffmann-La Roche at 21 sites in 3 countries.
Trial summary
This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment consisting of atezolizumab in combination with either obinutuzumab + bendamustine (Atezo-G-benda) or obinutuzumab + CHOP (Atezo-G-CHOP) in participants with FL and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma, Lymphoma Follicular
- What is being tested?
- Atezolizumab, Bendamustine and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- 21 sitesin 3 countries
- Study dates
- 22 Dec 2015to 8 May 2020
- 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
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- For participants enrolled in the safety run-in phase: lymphoma classified as either relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen or previously untreated Grade 1, 2, or 3a FL that requires treatment
- For participants enrolled in the expansion phase: lymphoma classified as either previously untreated Grade 1, 2, or 3a FL that requires treatment or previously untreated advanced DLBCL
- Histologically documented cluster of differentiation 20 (CD20) positive lymphoma
- Fluorodeoxyglucose-avid lymphoma
- At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters in its largest dimension by CT scan or magnetic resonance imaging)
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- Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
- For women who are not postmenopausal or surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than [<] 1 percent [%] per year during the treatment period and for at least 18 months after the last dose of study treatment for participants in the Atezo-G-benda and Atezo-G-CHOP treatment groups or for at least 12 months after the last dose of study treatment for participants in the Atezo-R-CHOP treatment group
- For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm
Who cannot join
- Histological evidence of transformation of FL into high-grade B-cell non-Hodgkin's lymphoma (NHL)
- Central nervous system lymphoma or leptomeningeal infiltration
- For participants with DLBCL: preplanned consolidative radiotherapy
- Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
- For participants with relapsed or refractory FL: prior allogeneic or autologous stem cell transplantation, anthracycline therapy, treatment with fludarabine or alemtuzumab within 12 months prior to Day 1 of Cycle 1, treatment with a monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate within 4 weeks prior to Day 1 of Cycle 1, radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
- History of solid organ transplantation
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- History of severe allergic or anaphylactic reaction or known sensitivity to humanized or murine monoclonal antibodies
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab, obinutuzumab, rituximab, or bendamustine formulation, including mannitol
- Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening
- History of progressive multifocal leukoencephalopathy
- Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1
- History of other malignancy, autoimmune disease, or any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results
- Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1, or anticipation of a major surgical procedure during the course of the study
- For participants who will be receiving CHOP: left ventricular ejection fraction (LVEF) <50% by multiple-gated acquisition (MUGA) scan or echocardiogram
- Inadequate hematologic, renal, and liver function (unless due to underlying lymphoma)
Trial locations and contacts
21 sites in 3 countries.
21 sites in 3 countries
United States9 sites
Rocky Mountain Cancer Center - Aurora
Aurora, Colorado, 80012
Texas Oncology
Austin, Texas, 78705
Texas Oncology-Tyler
Irving, Texas, 75063
University Miami
Miami, Florida, 33136
New York Uni Medical Center
New York, New York, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224
Oncology Associates of Oregon, P.C.; Willamette Valley Cancer Institute
Springfield, Oregon, 97477
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Italy7 sites
Asst Papa Giovanni XXIII
Bergamo, Lombardy, 24100
Azienda Ospedaliera S. Orsola-Malpighi
Bologna, Emilia-Romagna, 40138
Azienda Ospedaliera Univ
Florence, Tuscany, 50141
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
Meldola, Emilia-Romagna, 47014
Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia
Ravenna, Emilia-Romagna, 48100
Ospedale Infermi di Rimini
Rimini, Emilia-Romagna, 47900
AOU Città della Salute e della Scienza di Torino - Presidio Le Molinette
Torino, Lazio, 10126
Australia5 sites
Monash Medical Centre
Clayton, Victoria, 3168
Austin Hospital
Heidelberg, Victoria, 3084
Concord Repatriation General Hospital; Haematology
Sydney, New South Wales, 2139
Calvary Mater Newcastle
Waratah, New South Wales, 2298
The Queen Elizabeth Hospital; Haematology/Oncology
Woodville South, South Australia, 5011
About this study
Official title: A Phase IB/II Study Evaluating the Safety and Efficacy of Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus CHOP in Patients With Follicular Lymphoma or Rituximab Plus CHOP in Patients With Diffuse Large B-Cell Lymphoma
This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment consisting of atezolizumab in combination with either obinutuzumab + bendamustine (Atezo-G-benda) or obinutuzumab + CHOP (Atezo-G-CHOP) in participants with FL and atezolizumab + rituximab + chemotherapy (Atezo-R-CHOP) in participants with DLBCL, followed by post-induction treatment consisting of either atezolizumab plus obinutuzumab (Atezo-G) in participants with FL who achieve a complete response (CR) or partial response (PR) at end of induction (EOI) or atezolizumab alone in participants with DLBCL who achieve a CR at EOI.
- Being tested
- Atezolizumab, Bendamustine, Cyclophosphamide, Doxorubicin, Obinutuzumab
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called RO5541267; Tecentriq
Atezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25.
BendamustineDrug
Bendamustine will be administered at a dose of 90 milligrams per square meter (mg/m^2) IV on Days 1 and 2 of Cycles 1-6, during induction treatment.
CyclophosphamideDrug
Cyclophosphamide will be administered at a dose of 750 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.
DoxorubicinDrug
Doxorubicin will be administered at a dose of 50 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.
ObinutuzumabDrug
Also called RO5072759
Atezo-G-Benda: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6, during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6 during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1 during maintenance treatment.
PrednisoneDrug
Prednisone will be administered at a dose of 40 mg/m^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles).
VincristineDrug
Vincristine will be administered at a dose of 1.4 mg/m^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment.
RituximabDrug
Atezo-R-CHOP: Participants with previously untreated DLBCL will receive rituximab at a dose of 375 mg/m^2 IV on Day 1 of Cycle 1-8, during induction treatment.
| Study group | Role | What they receive |
|---|---|---|
| Atezo-G-Benda (Safety Run-In and Expansion Phases) | Experimental | Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL will receive same treatment regimen as described for safety run-in phase. Receives: Drug: Atezolizumab; Drug: Bendamustine; Drug: Obinutuzumab |
| Atezo-G-CHOP (Safety Run-In Phase) | Experimental | Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment. Receives: Drug: Atezolizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Obinutuzumab; Drug: Prednisone; Drug: Vincristine |
| Atezo-R-CHOP (Expansion Phase) | Experimental | Participants with previously untreated DLBCL will receive rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment. Receives: Drug: Atezolizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria
Primary end point was positron emission tomography (PET) CR at EOI by IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to [</=] mediastinum), or 3 (uptake less than [<] mediastinum but </=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. All PET evaluable 1L FL and 1L DLBCL participants with at least one dose of atezolizumab were included in efficacy population.
Measured: Up to approximately 6 months
Percentage of Participants With Adverse Events
An adverse event 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 adverse event 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.
Measured: Baseline up to approximately 4 years
Secondary outcomes (14)
Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Measured: Up to approximately 6 months
Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
Complete response according to the modified Cheson 2007 criteria using PET/CT scan: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. Partial Response (PR): at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Measured: Up to approximately 6 months
Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
Complete response according to modified Cheson 2007 criteria using PET/CT scan: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If bone marrow was involved by lymphoma prior to treatment, infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of other nodes, liver, or spleen; with exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population. Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy.
Measured: Up to approximately 6 months
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
Objective response: having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Measured: Up to approximately 6 months
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
Objective response: having CR or PR as assessed according to the modified response criteria for iNHL (Modified Cheson et al, 2007). CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Measured: Up to approximately 6 months
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Lugano 2014 Criteria
Tumor response assessment was performed by IRC according to modified Lugano classification using PET/CT scan. OR defined as a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with/without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR: a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Measured: Up to approximately 6 months
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR: a response of CR or PR. CR: a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes \& extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR with a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. All positron emission tomography (PET) evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Measured: Up to approximately 6 months
Percentage of Participants With Best Response of CR or PR During Study, as Determined by Investigator Using Modified Cheson 2007 Criteria
CR: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy, liver and spleen have returned to normal size (if enlarged at baseline), If the bone marrow was involved by lymphoma prior to treatment, the infiltrate must have cleared on repeat bone marrow biopsy. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites; no increase in the size of the other nodes, liver, or spleen; with the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present. Only Atezo-G-Benda and Atezo-R-Chop cohorts were evaluated for efficacy.
Measured: Baseline up to approximately 4 years (assessed at Baseline, 6 to 8 weeks after Day [D] 1 of Cycle [Cy] 6 or 8 (1Cy: 21 or 28 days), then every 2 months up to 24 months, at 35 days of last dose, and at every 3 months post-treatment follow-up [up 4 years])
Observed Serum Obinutuzumab Concentration
Predose time point was "any time prior to dose" for Cycle (Cy) 1 and "within 5 hour prior to dose" for other cycles (Cy 2,5,6) and for Months 1 to 24 during maintenance phase. Infusion duration for administration of first infusion should begin at an initial rate of 50 milligrams per hour (mg/hour). If no reaction occurs, increase the infusion rate in 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.
Measured: Induction: Predose, 0.5 hour (h) postinfusion on Day (D) 1 of Cy1,2,5,6 (1Cy: 21/28 days); Maintenance: Predose, 0.5h postinfusion on Day 1 of Month 1,3,7,15,23; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)
Observed Serum Atezolizumab Concentration
Atezo-G-Benda: Induction:Predose on D1 of Cy5,6 \& D1,15 of Cy2,3 (1Cy:21/28 days), Cy2D1:0.5h postinfusion; Maintenance:Predose on D1 of Month 1,2,4,7,15,23, Month 2 D1: 0.5h postinfusion; 120 days \& 1 year of last dose or at treatment discontinuation (up to 4 years); Atezo-G-CHOP: Induction:Predose on D1 of Cy2,3,5,6 (1Cy:21 days), Cy2D1:0.5h postinfusion; Maintenance:Predose on D1 of Month 1,2,3,4,7,15,23, Month 2 D1: 0.5h postinfusion; 120 days \& 1 year of last dose or at treatment discontinuation (up to 4 years). Predose time point was "within 5 hour prior to dose" for Cy2,3,5,6 during induction phase and for Months 1 to 24 during maintenance phase. infusion length: 30-60 minutes.
Measured: Atezo-R-CHOP: Predose on D1 of Cy2,3,5,8,9,10,11,12,16,20,25 (1Cy:21 days), 0.5h postinfusion of D1 of Cy2,9; at 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)
Observed Serum Rituximab Concentration
Predose time point was "any time prior to dose" for Cycle 1 and "within 5 hour prior to dose" for other cycles (Cycles 2,5,8) during induction phase and for Months 1 to 24 during maintenance phase. Infusion duration for administration of first infusion should begin at an initial rate of 50 mg/hour. If no infusion-related or hypersensitivity reaction occurs, increase the infusion rate in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour. If no reaction occurs, increase the infusion rate in 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.
Measured: Predose, 0.5h postinfusion on D1 of Cy1,2,5,8 (1Cy: 21 days); at 120 days and 1 year after last rituximab dose or at treatment discontinuation (up to 4 years)
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Induction: Predose (any time prior to dose) on D1 of Cy1,5,6 (1Cy: 21/28 days); Maintenance: Predose (any time prior to dose) on D1 of Month 1; at 120 days and 1 year of last obinutuzumab dose or at treatment discontinuation (up to 4 years)
Measured: Baseline up to approximately 4 years
Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Induction: Predose (any time prior to dose) on D1 of Cy1,5,8 (1Cy: 21 days); Maintenance: at 120 days and 1 year of last rituximab dose or at treatment discontinuation (up to 4 years)
Measured: Baseline up to approximately 4 years
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Atezo-G-CHOP: Induction: Predose on D1 of Cy2,3,5,6 (1 Cy: 21 days); Maintenance: Predose on D1 of Month 1,2,4,7,15,23; at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years); Atezo-R-CHOP: Predose on D1 of Cy 2,3,5,8,16,25 (1 Cy: 21 days); at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years). Predose time point was "any time prior to dose" for Cycles 2,3,5,6,8 during induction phase, for Cycles 16,25 during consolidation treatment, and for Months 1 to 24 during maintenance phase. Atezo-G-Benda: Induction: Predose on D1 of Cy2,3,5,6 (1Cy: 28 days), Cy3D15: Predose; ; Maintenance: Predose on D1 of Month 1,4,7,15,23; at 120 days and 1 year of last atezolizumab dose or at treatment discontinuation (up to 4 years). The percentage of participants with positive results for ATAs to atezolizumab at baseline and at post-baseline time points are reported.
Measured: Baseline up to approximately 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2015 (estimated)
- Study start22 Dec 2015
- Primary completion11 Apr 2018
- Study completion8 May 2020
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 Diffuse Large B-Cell Lymphoma, Lymphoma FollicularStudies 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
- 91 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
- NCT02596971
- Sponsor's protocol ID
- BO29563
- Other IDs
- 2015-001364-19, 2015
- Status last verified
- Apr 2021
- First submitted
- 3 Nov 2015
- Last updated
- 24 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Younes A, Burke JM, Cheson BD, Diefenbach CS, Ferrari S, Hahn UH, Hawkes EA, Khan C, Lossos IS, Musuraca G, Tani M, Vitolo U, Yuen S, Raval A, Shivhare M, Nielsen TG, Sellam G, Sharman JP. Safety and efficacy of atezolizumab with rituximab and CHOP in previously untreated diffuse large B-cell lymphoma. Blood Adv. 2023 Apr 25;7(8):1488-1495. doi: 10.1182/bloodadvances.2022008344.
PubMed 36287231Younes A, Burke JM, Diefenbach C, Ferrari S, Khan C, Sharman JP, Tani M, Ujjani C, Vitolo U, Yuen S, Raval A, Shivhare M, Nielsen TG, Sellam G, Gilbertson M. Safety and efficacy of atezolizumab with obinutuzumab and bendamustine in previously untreated follicular lymphoma. Blood Adv. 2022 Oct 25;6(20):5659-5667. doi: 10.1182/bloodadvances.2021006131.
PubMed 35359000
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2021. 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 Atezolizumab in Combination With Either Obinutuzumab Plus Bendamustine or Obinutuzumab Plus CHOP in Patients With Follicular Lymphoma or Rituximab Plus CHOP in Patients With Diffuse Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT02596971
- Acronym / sponsor ID
- BO29563
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 22 Dec 2015 (actual)
- Primary completion
- 11 Apr 2018 (actual)
- Study completion
- 8 May 2020 (actual)
- First posted
- 4 Nov 2015 (estimated)
- Results
- Posted 13 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase Ib/II, open-label, multicenter, non-randomized study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment consisting of atezolizumab in combination with either obinutuzumab + bendamustine (Atezo-G-benda) or obinutuzumab + CHOP (Atezo-G-CHOP) in participants with FL and atezolizumab + rituximab + chemotherapy (Atezo-R-CHOP) in participants with DLBCL, followed by post-induction treatment consisting of either atezolizumab plus obinutuzumab (Atezo-G) in participants with FL who achieve a complete response (CR) or partial response (PR) at end of induction (EOI) or atezolizumab alone in participants with DLBCL who achieve a CR at EOI.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Atezo-G-Benda (Safety Run-In and Expansion Phases) | Experimental | Drug: Atezolizumab, Drug: Bendamustine, Drug: ObinutuzumabSafety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month [q2m]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL will receive same treatment regimen as described for safety run-in phase. |
| Atezo-G-CHOP (Safety Run-In Phase) | Experimental | Drug: Atezolizumab, Drug: Cyclophosphamide, Drug: Doxorubicin, Drug: Obinutuzumab, Drug: Prednisone, Drug: VincristineSafety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment. |
| Atezo-R-CHOP (Expansion Phase) | Experimental | Drug: Atezolizumab, Drug: Cyclophosphamide, Drug: Doxorubicin, Drug: Prednisone, Drug: Vincristine, Drug: RituximabParticipants with previously untreated DLBCL will receive rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- For participants enrolled in the safety run-in phase: lymphoma classified as either relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen or previously untreated Grade 1, 2, or 3a FL that requires treatment
- For participants enrolled in the expansion phase: lymphoma classified as either previously untreated Grade 1, 2, or 3a FL that requires treatment or previously untreated advanced DLBCL
- Histologically documented cluster of differentiation 20 (CD20) positive lymphoma
- Fluorodeoxyglucose-avid lymphoma
Key exclusion criteria (15 listed)
- Histological evidence of transformation of FL into high-grade B-cell non-Hodgkin's lymphoma (NHL)
- Central nervous system lymphoma or leptomeningeal infiltration
- For participants with DLBCL: preplanned consolidative radiotherapy
- Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
- For participants with relapsed or refractory FL: prior allogeneic or autologous stem cell transplantation, anthracycline therapy, treatment with fludarabine or alemtuzumab within 12 months prior to Day 1 of Cycle 1, treatment with a monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate within 4 weeks prior to Day 1 of Cycle 1, radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks 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 |
|---|---|---|
| AtezolizumabAlso: RO5541267; TecentriqAtezo-G-Benda: Atezolizumab 840 milligrams (mg) intravenously (IV) on Days 1 and 15 of Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-6, during induction treatment, followed by 840 mg IV on Days 1 and 2 of each month, starting with Month 1. Atezo-R-CHOP: Atezolizumab 1200 mg IV on Day 1 Cycles 2-8, during induction treatment, followed by 1200 mg IV on Day 1 of Cycles 9-25. | Drug | Atezo-G-Benda (Safety Run-In and Expansion Phases), Atezo-G-CHOP (Safety Run-In Phase), Atezo-R-CHOP (Expansion Phase) |
| BendamustineBendamustine will be administered at a dose of 90 milligrams per square meter (mg/m^2) IV on Days 1 and 2 of Cycles 1-6, during induction treatment. | Drug | Atezo-G-Benda (Safety Run-In and Expansion Phases) |
| CyclophosphamideCyclophosphamide will be administered at a dose of 750 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment. | Drug | Atezo-G-CHOP (Safety Run-In Phase), Atezo-R-CHOP (Expansion Phase) |
| DoxorubicinDoxorubicin will be administered at a dose of 50 mg/m^2 IV on Day 1 of Cycle 1-6/8, during induction treatment. | Drug | Atezo-G-CHOP (Safety Run-In Phase), Atezo-R-CHOP (Expansion Phase) |
| ObinutuzumabAlso: RO5072759Atezo-G-Benda: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6, during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1, during maintenance treatment. Atezo-G-CHOP: Obinutuzumab will be administered at a dose of 1000 mg IV on Days 1, 8, and 15 of Cycle 1 and 1000 mg IV on Day 1 of Cycles 2-6 during induction treatment, followed by 1000 mg IV on Day 1 of every other month, starting with Month 1 during maintenance treatment. | Drug | Atezo-G-Benda (Safety Run-In and Expansion Phases), Atezo-G-CHOP (Safety Run-In Phase) |
| PrednisonePrednisone will be administered at a dose of 40 mg/m^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles). | Drug | Atezo-G-CHOP (Safety Run-In Phase), Atezo-R-CHOP (Expansion Phase) |
| VincristineVincristine will be administered at a dose of 1.4 mg/m^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment. | Drug | Atezo-G-CHOP (Safety Run-In Phase), Atezo-R-CHOP (Expansion Phase) |
| RituximabAtezo-R-CHOP: Participants with previously untreated DLBCL will receive rituximab at a dose of 375 mg/m^2 IV on Day 1 of Cycle 1-8, during induction treatment. | Drug | Atezo-R-CHOP (Expansion Phase) |
Primary outcome
Percentage of Participants With Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria
Time frame: Up to approximately 6 months
Primary end point was positron emission tomography (PET) CR at EOI by IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to [</=] mediastinum), or 3 (uptake less than [<] mediastinum but </=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. All PET evaluable 1L FL and 1L DLBCL participants with at least one dose of atezolizumab were included in efficacy population.
Percentage of Participants With Adverse Events
Time frame: Baseline up to approximately 4 years
An adverse event 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 adverse event 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.
14 secondary outcomes
Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
Time frame: Up to approximately 6 months
Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
Time frame: Up to approximately 6 months
Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
Time frame: Up to approximately 6 months
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
Time frame: Up to approximately 6 months
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
Time frame: Up to approximately 6 months
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Lugano 2014 Criteria
Time frame: Up to approximately 6 months
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
Time frame: Up to approximately 6 months
Percentage of Participants With Best Response of CR or PR During Study, as Determined by Investigator Using Modified Cheson 2007 Criteria
Time frame: Baseline up to approximately 4 years (assessed at Baseline, 6 to 8 weeks after Day [D] 1 of Cycle [Cy] 6 or 8 (1Cy: 21 or 28 days), then every 2 months up to 24 months, at 35 days of last dose, and at every 3 months post-treatment follow-up [up 4 years])
Observed Serum Obinutuzumab Concentration
Time frame: Induction: Predose, 0.5 hour (h) postinfusion on Day (D) 1 of Cy1,2,5,6 (1Cy: 21/28 days); Maintenance: Predose, 0.5h postinfusion on Day 1 of Month 1,3,7,15,23; 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)
Observed Serum Atezolizumab Concentration
Time frame: Atezo-R-CHOP: Predose on D1 of Cy2,3,5,8,9,10,11,12,16,20,25 (1Cy:21 days), 0.5h postinfusion of D1 of Cy2,9; at 120 days & 1 year of last dose or at treatment discontinuation (up to 4 years)
Observed Serum Rituximab Concentration
Time frame: Predose, 0.5h postinfusion on D1 of Cy1,2,5,8 (1Cy: 21 days); at 120 days and 1 year after last rituximab dose or at treatment discontinuation (up to 4 years)
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Time frame: Baseline up to approximately 4 years
Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Time frame: Baseline up to approximately 4 years
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Time frame: Baseline up to approximately 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36287231Younes A, Burke JM, Cheson BD, Diefenbach CS, Ferrari S, Hahn UH, Hawkes EA, Khan C, Lossos IS, Musuraca G, Tani M, Vitolo U, Yuen S, Raval A, Shivhare M, Nielsen TG, Sellam G, Sharman JP. Safety and efficacy of atezolizumab with rituximab and CHOP in previously untreated diffuse large B-cell lymphoma. Blood Adv. 2023 Apr 25;7(8):1488-1495. doi: 10.1182/bloodadvances.2022008344.
- Derived from this study: PubMed 35359000Younes A, Burke JM, Diefenbach C, Ferrari S, Khan C, Sharman JP, Tani M, Ujjani C, Vitolo U, Yuen S, Raval A, Shivhare M, Nielsen TG, Sellam G, Gilbertson M. Safety and efficacy of atezolizumab with obinutuzumab and bendamustine in previously untreated follicular lymphoma. Blood Adv. 2022 Oct 25;6(20):5659-5667. doi: 10.1182/bloodadvances.2021006131.
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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
21 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 Atezolizumab, Bendamustine and Cyclophosphamide in people with Diffuse Large B-Cell Lymphoma, Lymphoma Follicular, run by Hoffmann-La Roche at 21 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 9 inclusion and 15 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 24 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Italy, Australia. 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 13 Jun 2019). 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 Complete Response (CR) at End of Induction (EOI), as Determined by the Independent Review Committee (IRC) Using Modified Lugano 2014 Criteria (time frame: Up to approximately 6 months). The study lists 2 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 NCT02596971, 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 24 May 2021.