Clinical trial NCT02611323: A Study of Obinutuzumab, Rituximab, Polatuzumab Vedotin, and Venetoclax in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)
Official title: A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Polatuzumab Vedotin and Venetoclax in Patients With Relapsed or Refractory Follicular Lymphoma and Rituximab in Combination With Polatuzumab Vedotin and Venetoclax in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-11-20
Enrollment: 133
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 study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment with obinutuzumab, polatuzumab vedotin, and venetoclax in participants with relapsed or refractory FL, and with rituximab, polatuzumab vedotin, and venetoclax in participants with DLBCL. Participants with FL who achieve complete response (CR), partial response (PR), or stable disease (SD) at the end of induction therapy will receive post-induction treatment with obinutuzumab and venetoclax, and participants with DLBCL who achieve CR or PR at the end of induction (EOI) will receive post-induction treatment with rituximab and venetoclax.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* For obinutuzumab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) (anti-CD20) monoclonal antibody (mAb) and for which no other more appropriate treatment option exists, as determined by the investigator
* For rituximab + polatuzumab vedotin + venetoclax treatment group, relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 mAb and for which no curative option exists as determined by the investigator
* At least one bidimensionally measurable lesion

Exclusion Criteria:

* Known CD20-negative status at relapse or progression
* Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
* Grade 3b FL
* History of transformation of indolent disease to DLBCL
* Current use of systemic corticosteroids greater than (\>) 20 mg prednisone per day (or equivalent); or prior anti-cancer therapy to include: 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
* Central nervous system (CNS) disease
* Active infection
* Actual or potential cytochrome P450 (CYP) 3A interactions including: requirement for warfarin; use of strong and moderate CYP3A inhibitors or inducers within 7 days prior to first dose of venetoclax; or consumption of grapefruit, Seville oranges, or star fruit within 3 days prior to first dose of venetoclax
* 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 \<3 months

Primary outcomes:
measure: Percentage of Participants With CR at EOI Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography (PET) and Computed Tomography (CT) Scans
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21 days)
measure: FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From study start to 24 months after last dose of study drug (approximately 56 months)
measure: DLBCL Cohorts: Percentage of Participants With AEs and SAEs
timeFrame: From study start to 3 months after last dose of study drug (approximately 21 months)
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
measure: RP2D of Polatuzumab Vedotin
timeFrame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
measure: RP2D of Venetoclax
timeFrame: Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Secondary outcomes:
measure: Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
measure: Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
measure: Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
measure: Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
measure: Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
measure: Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
measure: Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone
timeFrame: 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
measure: Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
timeFrame: Up to every 6 months until disease progression, the start of new anti-lymphoma treatment, or the end of the study, whichever occurs first (approximately 77 months)
measure: Observed Serum Obinutuzumab Concentration
timeFrame: Pre-dose & 0.5 hours post-dose on Day 1 Cycles 1, 2, 4, & 6; and pre-dose on Day 1 of Months 2, 8, 14, 20; study drug discontinuation, Day 120 &1 year post-last dose (up to approximately 40 months) (1 cycle = 21 days)
measure: Observed Serum Rituximab Concentration
timeFrame: Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1 and 6; pre-dose on Day 1 of Cycles 2 and 4; (1 cycle = 21 days)
measure: Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin
timeFrame: Pre-dose on Day 1 of Cycles 1, 2 and 4; study drug discontinuation visit; Day 120 and 1 year post-last dose (up to approximately 16 months) (1 cycle=21 days)
measure: Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)
timeFrame: Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days)
measure: Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE
timeFrame: Pre-dose and 0.5 hours post-dose on Day 1 of Cycles 1, 2 and 4; post-dose on Days 8 and 15 of Cycle 1; predose on Day 1 of Cycle 6 (1 cycle=21 days)
measure: Observed Plasma Venetoclax Concentration
timeFrame: Pre-dose and 4 hours post-dose on Day 1 Cycle 1, pre-dose & 2, 4, 6, & 8 hours post-dose on Day 1 Cycle 2, pre-dose & 4hours post-dose on Day 1 Cycle 4 & pre-dose on Day 1 Cycle 6; (1 cycle = 21 days)
measure: Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
timeFrame: Baseline up to approximately 2 years after last dose (up to approximately 56 months)
measure: Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin
timeFrame: Baseline up to 1 year post last dose (up to approximately 16 months)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Pembroke
country: United States
facility: Memorial Healthcare System
state: Florida
city: Atlanta
country: United States
facility: Emory Univ Winship Cancer Inst
state: Georgia
city: Louisville
country: United States
facility: University of Louisville Hospital; The James Graham Brown Cancer Center
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Inst.
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Temple
country: United States
facility: Scott and White
state: Texas
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital; Haematology Department
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: North Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Bergamo
country: Italy
facility: Papa Giovanni Hospital XXIII
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: UO Ematologia, Ospedale S.Maria delle Croci
state: Emilia-Romagna
city: Rimini
country: Italy
facility: Ospedale Infermi U.O. Ematologia
state: Emilia-Romagna
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: Lombardia
city: Novara
country: Italy
facility: SCDU Ematologia
state: Piemonte
city: Torino
country: Italy
facility: A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
state: Piemonte
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: