Clinical trial NCT02596971: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B-Cell Lymphoma, Lymphoma Follicular
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-11-04
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.


Eligibility criteria: 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

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)

Primary outcomes:
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
timeFrame: Up to approximately 6 months
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to approximately 4 years
Secondary outcomes:
measure: Percentage of Participants With CR at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
timeFrame: Up to approximately 6 months
measure: Percentage of Participants With CR at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
timeFrame: Up to approximately 6 months
measure: Percentage of Participants With CR at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
timeFrame: Up to approximately 6 months
measure: Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Modified Cheson 2007 Criteria
timeFrame: Up to approximately 6 months
measure: Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Modified Cheson 2007 Criteria
timeFrame: Up to approximately 6 months
measure: Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the IRC Using Lugano 2014 Criteria
timeFrame: Up to approximately 6 months
measure: Percentage of Participants With Objective Response (CR or PR) at EOI, as Determined by the Investigator Using Lugano 2014 Criteria
timeFrame: Up to approximately 6 months
measure: Percentage of Participants With Best Response of CR or PR During Study, as Determined by Investigator Using Modified Cheson 2007 Criteria
timeFrame: 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])
measure: Observed Serum Obinutuzumab Concentration
timeFrame: 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)
measure: Observed Serum Atezolizumab Concentration
timeFrame: 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)
measure: Observed Serum Rituximab Concentration
timeFrame: 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)
measure: Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
timeFrame: Baseline up to approximately 4 years
measure: Percentage of Participants With Human Anti-Chimeric Antibodies (HACAs) to Rituximab
timeFrame: Baseline up to approximately 4 years
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
timeFrame: Baseline up to approximately 4 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Rocky Mountain Cancer Center - Aurora
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University Miami
state: Florida
city: New York
country: United States
facility: New York Uni Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Springfield
country: United States
facility: Oncology Associates of Oregon, P.C.; Willamette Valley Cancer Institute
state: Oregon
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Irving
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Sydney
country: Australia
facility: Concord Repatriation General Hospital; Haematology
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital; Haematology/Oncology
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Bologna
country: Italy
facility: Azienda Ospedaliera S. Orsola-Malpighi
state: Emilia-Romagna
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
state: Emilia-Romagna
city: Ravenna
country: Italy
facility: Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia
state: Emilia-Romagna
city: Rimini
country: Italy
facility: Ospedale Infermi di Rimini
state: Emilia-Romagna
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino - Presidio Le Molinette
state: Lazio
city: Bergamo
country: Italy
facility: Asst Papa Giovanni XXIII
state: Lombardia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Univ
state: Toscana
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Younes 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.