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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02596971




Registration number
NCT02596971
Ethics application status
Date submitted
3/11/2015
Date registered
4/11/2015
Date last updated
24/05/2021

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
2015-001364-19
Secondary ID [2] 0 0
BO29563
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B-Cell Lymphoma, Lymphoma Follicular 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Bendamustine
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Prednisone
Treatment: Drugs - Vincristine
Treatment: Drugs - Rituximab

Experimental: Atezo-G-Benda (Safety Run-In and Expansion Phases) - 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.

Experimental: Atezo-G-CHOP (Safety Run-In Phase) - 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.

Experimental: Atezo-R-CHOP (Expansion Phase) - 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.


Treatment: Drugs: Atezolizumab
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.

Treatment: Drugs: Bendamustine
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.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide will be administered at a dose of 750 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Treatment: Drugs: Doxorubicin
Doxorubicin will be administered at a dose of 50 mg/m\^2 IV on Day 1 of Cycle 1-6/8, during induction treatment.

Treatment: Drugs: Obinutuzumab
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.

Treatment: Drugs: Prednisone
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).

Treatment: Drugs: Vincristine
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.

Treatment: Drugs: Rituximab
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Up to approximately 6 months
Primary outcome [2] 0 0
Percentage of Participants With Adverse Events
Timepoint [2] 0 0
Baseline up to approximately 4 years
Secondary outcome [1] 0 0
Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
Timepoint [1] 0 0
Up to approximately 6 months
Secondary outcome [2] 0 0
Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
Timepoint [2] 0 0
Up to approximately 6 months
Secondary outcome [3] 0 0
Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
Timepoint [3] 0 0
Up to approximately 6 months
Secondary outcome [4] 0 0
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
Timepoint [4] 0 0
Up to approximately 6 months
Secondary outcome [5] 0 0
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
Timepoint [5] 0 0
Up to approximately 6 months
Secondary outcome [6] 0 0
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Lugano 2014 Criteria
Timepoint [6] 0 0
Up to approximately 6 months
Secondary outcome [7] 0 0
Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
Timepoint [7] 0 0
Up to approximately 6 months
Secondary outcome [8] 0 0
Percentage of Participants With Best Response of CR or PR During Study, as Determined by Investigator Using Modified Cheson 2007 Criteria
Timepoint [8] 0 0
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])
Secondary outcome [9] 0 0
Observed Serum Obinutuzumab Concentration
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Observed Serum Atezolizumab Concentration
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Observed Serum Rituximab Concentration
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Timepoint [12] 0 0
Baseline up to approximately 4 years
Secondary outcome [13] 0 0
Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
Timepoint [13] 0 0
Baseline up to approximately 4 years
Secondary outcome [14] 0 0
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Timepoint [14] 0 0
Baseline up to approximately 4 years

Eligibility
Key inclusion criteria
* 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)
* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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
* 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital; Haematology - Sydney
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital; Haematology/Oncology - Woodville South
Recruitment hospital [4] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [5] 0 0
Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 0 0
2139 - Sydney
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
5011 - Woodville South
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Italy
State/province [8] 0 0
Emilia-Romagna
Country [9] 0 0
Italy
State/province [9] 0 0
Lazio
Country [10] 0 0
Italy
State/province [10] 0 0
Lombardia
Country [11] 0 0
Italy
State/province [11] 0 0
Toscana

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.