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A Study of Obinutuzumab, Rituximab, Polatuzumab Vedotin, and Venetoclax in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)

Primary Purpose

Non-Hodgkin's Lymphoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Obinutuzumab
Rituximab
Polatuzumab Vedotin
Venetoclax
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 milligrams (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

Sites / Locations

  • University of Arizona Cancer Center
  • Yale Cancer Center
  • Memorial Healthcare System
  • Emory Univ Winship Cancer Inst
  • University of Louisville Hospital; The James Graham Brown Cancer Center
  • University of Michigan
  • Rutgers Cancer Institute of New Jersey
  • Roswell Park Cancer Inst.
  • Fox Chase Cancer Center
  • Scott and White
  • Royal North Shore Hospital; Haematology Department
  • Calvary Mater Newcastle
  • Princess Alexandra Hospital
  • The Queen Elizabeth Hospital
  • Royal Hobart Hospital
  • Peter MacCallum Cancer Center
  • Papa Giovanni Hospital XXIII
  • Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
  • UO Ematologia, Ospedale S.Maria delle Croci
  • Ospedale Infermi U.O. Ematologia
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • SCDU Ematologia
  • A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose-Escalation Cohort: FL

Dose-Escalation Cohort: DLBCL

Expansion Cohort: FL

Expansion Cohort: DLBCL

Arm Description

Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and venetoclax when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.

Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at escalating doses to identify the RP2D of venetoclax when combined with fixed doses of polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.

Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at the RP2D identified during the dose-escalation phase, in addition to obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.

Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at the RP2D identified during the dose-escalation phase, in addition to polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.

Outcomes

Primary Outcome Measures

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
CR at EOI was assessed by the IRC according to modified Lugano Response Criteria (MLRC) for Malignant Lymphoma 2014 using PET-CT scan. Per MLRC, CR was defined as complete metabolic response (MR) in lymph nodes and extra lymphatic sites (ELS) with a score of 1, 2, or 3, with or without a residual mass on PET 5-point scale (5-PS), 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 fluorodeoxyglucose (FDG)-avid disease in bone marrow. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was defined as 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 could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE was defined as any AE that was fatal, life threatening, requires prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0). Percentages have been rounded off to the first decimal point.
DLBCL Cohorts: Percentage of Participants With AEs and SAEs
An AE was defined as 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 could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE was defined as any AE that was fatal, life threatening, requires prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the NCI-CTCAE, v4.0. Percentages have been rounded off to the first decimal point.
Number of Participants With Dose-Limiting Toxicities (DLTs)
DLT=any one of the events that occurred in first treatment cycle & per the investigator was related to study treatment. Any AE that lead to a delay of > 14 days in start of next treatment cycle; Any Grade 3/4 non-hematologic AE with few exceptions; Any increase in hepatic transaminase >3×baseline(BL) & increase in direct bilirubin >2×upper limit of normal (ULN), without any findings of cholestasis/jaundice/signs of hepatic dysfunction & in absence of other contributory factors; Grade1 alanine transaminase (ALT)/aspartate transaminase (AST) elevation at BL as result of liver metastases, only a Grade ≥3 elevation, also ≥3×BL lasting >7 days; Hematologic AE meeting protocol specified criteria. Events were graded per NCI CTCAE v4.0. Grade 1:Mild; asymptomatic/mild symptoms; Grade 2:Moderate;minimal,local/non-invasive intervention indicated; Grade 3:Severe/medically significant, but not immediately life-threatening; Grade 4:Life-threatening consequences/urgent intervention indicated.
RP2D of Polatuzumab Vedotin
RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of polatuzumab vedotin when given in combination with fixed dose of obinutuzumab in participants with FL was determined.
RP2D of Venetoclax
RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of venetoclax when given in combination with fixed dose of polatuzumab vedotin in participants with FL and DLBCL was determined.

Secondary Outcome Measures

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. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
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 centimeters (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, immunohistochemistry (IHC) negative. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Percentage of Participants With CR at EOI, Determined by the 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. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans
OR=percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT=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. PR based on PET-CT=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 (suggest responding disease) or at end of treatment (indicate residual disease), residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). 90% CI was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans
OR=percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT=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. PR based on PET-CT=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 (suggest responding disease) or at end of treatment (indicate residual disease), residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). 90% CI was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Percentage of Participants With OR at EOI, Determined by an 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, no new sites of lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Percentage of Participants With OR at EOI, 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 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, no new sites of lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
BOR=CR or PR as assessed by investigator 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, no new sites of lesions. Percentages have been rounded off to the first decimal point.
Observed Serum Obinutuzumab Concentration
Observed Serum Rituximab Concentration
Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin
Total antibody is an analyte of polatuzumab vedotin.
Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)
acMMAE is an analyte of polatuzumab vedotin.
Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE
MMAE is an analyte of polatuzumab vedotin.
Observed Plasma Venetoclax Concentration
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.
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.

Full Information

First Posted
November 19, 2015
Last Updated
September 15, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02611323
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
March 9, 2016 (Actual)
Primary Completion Date
August 4, 2022 (Actual)
Study Completion Date
August 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
133 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose-Escalation Cohort: FL
Arm Type
Experimental
Arm Description
Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at escalating doses to identify the recommended Phase 2 dose (RP2D) for polatuzumab vedotin and venetoclax when combined with a fixed dose of obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Arm Title
Dose-Escalation Cohort: DLBCL
Arm Type
Experimental
Arm Description
Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at escalating doses to identify the RP2D of venetoclax when combined with fixed doses of polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
Arm Title
Expansion Cohort: FL
Arm Type
Experimental
Arm Description
Participants with relapsed or refractory FL will receive 18 weeks of induction treatment with polatuzumab vedotin and venetoclax at the RP2D identified during the dose-escalation phase, in addition to obinutuzumab. Those who achieve CR, PR, or SD at the EOI will be eligible to receive a 24-month maintenance regimen consisting of 8 months of venetoclax and 24 months of obinutuzumab.
Arm Title
Expansion Cohort: DLBCL
Arm Type
Experimental
Arm Description
Participants with relapsed or refractory DLBCL will receive 18 weeks of induction treatment. Venetoclax will be administered at the RP2D identified during the dose-escalation phase, in addition to polatuzumab vedotin and rituximab. Those who achieve CR or PR at the EOI will be eligible to receive an 8-month consolidation regimen consisting of venetoclax and rituximab.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
Participants will receive a fixed dose of obinutuzumab, 1000 milligrams (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. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 1000 mg via IV infusion on Day 1 of every other month (starting from Month 2) for up to 24 months, until disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Participants will receive a fixed dose of rituximab, 375 milligrams per square meter (mg/m^2) via IV infusion to be given on Day 1 of Cycles 1 to 6. Cycle length will be 21 days. For eligible participants, post-induction treatment may be given at a dose of 375 mg/m^2 via IV infusion on Day 1 of every other month (starting from Month 2) for up to 8 months, until disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Polatuzumab Vedotin
Intervention Description
Participants will receive polatuzumab vedotin via IV infusion at doses of 1.4 or 1.8 milligrams per kilogram (mg/kg) (for FL), and 1.8 mg/kg (for DLBCL) on Day 1 of each 21-day cycle for up to 18 weeks during induction treatment. Polatuzumab vedotin will not be given during the post-induction period.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Intervention Description
Participants will receive venetoclax film-coated tablets at doses of 200, 400, 600, or 800 mg (for FL), and 400, 600, or 800 mg (for DLBCL) on Days 1 to 21 of each 21-day cycle. Post-induction venetoclax may continue for up to 8 months, until disease progression or unacceptable toxicity.
Primary Outcome Measure Information:
Title
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
Description
CR at EOI was assessed by the IRC according to modified Lugano Response Criteria (MLRC) for Malignant Lymphoma 2014 using PET-CT scan. Per MLRC, CR was defined as complete metabolic response (MR) in lymph nodes and extra lymphatic sites (ELS) with a score of 1, 2, or 3, with or without a residual mass on PET 5-point scale (5-PS), 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 fluorodeoxyglucose (FDG)-avid disease in bone marrow. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Time Frame
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21 days)
Title
FL Cohorts: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE was defined as 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 could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE was defined as any AE that was fatal, life threatening, requires prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0). Percentages have been rounded off to the first decimal point.
Time Frame
From study start to 24 months after last dose of study drug (approximately 56 months)
Title
DLBCL Cohorts: Percentage of Participants With AEs and SAEs
Description
An AE was defined as 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 could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any new disease or worsening of an existing disease were also considered as AEs. An SAE was defined as any AE that was fatal, life threatening, requires prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to a mother exposed to study treatment. AEs and SAEs were reported based on the NCI-CTCAE, v4.0. Percentages have been rounded off to the first decimal point.
Time Frame
From study start to 3 months after last dose of study drug (approximately 21 months)
Title
Number of Participants With Dose-Limiting Toxicities (DLTs)
Description
DLT=any one of the events that occurred in first treatment cycle & per the investigator was related to study treatment. Any AE that lead to a delay of > 14 days in start of next treatment cycle; Any Grade 3/4 non-hematologic AE with few exceptions; Any increase in hepatic transaminase >3×baseline(BL) & increase in direct bilirubin >2×upper limit of normal (ULN), without any findings of cholestasis/jaundice/signs of hepatic dysfunction & in absence of other contributory factors; Grade1 alanine transaminase (ALT)/aspartate transaminase (AST) elevation at BL as result of liver metastases, only a Grade ≥3 elevation, also ≥3×BL lasting >7 days; Hematologic AE meeting protocol specified criteria. Events were graded per NCI CTCAE v4.0. Grade 1:Mild; asymptomatic/mild symptoms; Grade 2:Moderate;minimal,local/non-invasive intervention indicated; Grade 3:Severe/medically significant, but not immediately life-threatening; Grade 4:Life-threatening consequences/urgent intervention indicated.
Time Frame
Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Title
RP2D of Polatuzumab Vedotin
Description
RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of polatuzumab vedotin when given in combination with fixed dose of obinutuzumab in participants with FL was determined.
Time Frame
Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Title
RP2D of Venetoclax
Description
RP2D was defined as the highest dose with acceptable toxicity as determined from dose-escalation phase. The RP2D of venetoclax when given in combination with fixed dose of polatuzumab vedotin in participants with FL and DLBCL was determined.
Time Frame
Day 1 of Cycle 1 to Day 1 of Cycle 2 (1 cycle=21 days) in dose-escalation phase
Secondary Outcome Measure Information:
Title
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of PET-CT Scans
Description
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. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Time Frame
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Title
Percentage of Participants With CR at EOI, Determined by the IRC on the Basis of CT Scans Alone
Description
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 centimeters (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, immunohistochemistry (IHC) negative. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Time Frame
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Title
Percentage of Participants With CR at EOI, Determined by the Investigator on the Basis of CT Scans Alone
Description
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. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Time Frame
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Title
Percentage of Participants With Objective Response (OR) at EOI, Determined by an IRC on the Basis of PET and CT Scans
Description
OR=percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT=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. PR based on PET-CT=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 (suggest responding disease) or at end of treatment (indicate residual disease), residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). 90% CI was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Time Frame
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Title
Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of PET and CT Scans
Description
OR=percentage of participants with CR or PR as assessed by the IRC according to MLRC. Per MLRC CR based on PET-CT=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. PR based on PET-CT=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 (suggest responding disease) or at end of treatment (indicate residual disease), residual uptake higher than uptake in normal bone marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). 90% CI was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Time Frame
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Title
Percentage of Participants With OR at EOI, Determined by an IRC on the Basis of CT Scans Alone
Description
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, no new sites of lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Time Frame
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Title
Percentage of Participants With OR at EOI, Determined by the Investigator on the Basis of CT Scans Alone
Description
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 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, no new sites of lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method. Percentages have been rounded off to the first decimal point.
Time Frame
6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 23 weeks) (1 cycle=21days)
Title
Percentage of Participants With Best Overall Response (BOR) of CR or PR, Determined by the Investigator on the Basis of CT Scans Alone
Description
BOR=CR or PR as assessed by investigator 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, no new sites of lesions. Percentages have been rounded off to the first decimal point.
Time Frame
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)
Title
Observed Serum Obinutuzumab Concentration
Time Frame
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)
Title
Observed Serum Rituximab Concentration
Time Frame
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)
Title
Observed Serum Concentration of Total Antibody to Polatuzumab Vedotin
Description
Total antibody is an analyte of polatuzumab vedotin.
Time Frame
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)
Title
Observed Plasma Concentration of Polatuzumab Vedotin Antibody-Conjugated Mono-Methyl Auristatin E (MMAE) (acMMAE)
Description
acMMAE is an analyte of polatuzumab vedotin.
Time Frame
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)
Title
Observed Plasma Concentration of Polatuzumab Vedotin Unconjugated MMAE
Description
MMAE is an analyte of polatuzumab vedotin.
Time Frame
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)
Title
Observed Plasma Venetoclax Concentration
Time Frame
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)
Title
Number of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab
Description
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.
Time Frame
Baseline up to approximately 2 years after last dose (up to approximately 56 months)
Title
Number of Participants With Anti-Therapeutic Antibodies (ATAs) to Polatuzumab Vedotin
Description
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.
Time Frame
Baseline up to 1 year post last dose (up to approximately 16 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Memorial Healthcare System
City
Pembroke
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Facility Name
Emory Univ Winship Cancer Inst
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Louisville Hospital; The James Graham Brown Cancer Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0934
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Roswell Park Cancer Inst.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Scott and White
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Royal North Shore Hospital; Haematology Department
City
St. Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Calvary Mater Newcastle
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
The Queen Elizabeth Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Peter MacCallum Cancer Center
City
North Melbourne
State/Province
Victoria
ZIP/Postal Code
3051
Country
Australia
Facility Name
Papa Giovanni Hospital XXIII
City
Bergamo
State/Province
Emilia-Romagna
ZIP/Postal Code
24127
Country
Italy
Facility Name
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
City
Meldola
State/Province
Emilia-Romagna
ZIP/Postal Code
47014
Country
Italy
Facility Name
UO Ematologia, Ospedale S.Maria delle Croci
City
Ravenna
State/Province
Emilia-Romagna
ZIP/Postal Code
48121
Country
Italy
Facility Name
Ospedale Infermi U.O. Ematologia
City
Rimini
State/Province
Emilia-Romagna
ZIP/Postal Code
47923
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
Facility Name
SCDU Ematologia
City
Novara
State/Province
Piemonte
ZIP/Postal Code
28100
Country
Italy
Facility Name
A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

A Study of Obinutuzumab, Rituximab, Polatuzumab Vedotin, and Venetoclax in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)

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