Back to resultsA Study of Obinutuzumab in Combination With Idasanutlin and Venetoclax in Participants With Relapsed or Refractory (R/R) Follicular Lymphoma (FL) or Rituximab in Combination With Idasanutlin and Venetoclax in Participants With R/R Diffuse Large B-Cell Lymphoma (DLBCL)
Primary Purpose
Follicular Lymphoma, Lymphoma, Large B-Cell, Diffuse
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Idasanutlin
Obinutuzumab
Venetoclax
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Follicular Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- B-cell lymphoma classified as either of the following: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) monoclonal antibody; R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in participants who are not eligible for second line combination chemotherapy and autologous stem-cell transplantation, have failed second line combination chemotherapy, or experienced disease progression following autologous stem-cell transplantation
- Histologically documented CD20-positive lymphoma
- Fluorodeoxyglucose (FDG)-avid lymphoma (that is [i.e.], PET-positive lymphoma)
- At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension by CT scan or magnetic resonance imaging [MRI])
- Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
Exclusion Criteria:
- Known CD20-negative status at relapse or progression
- Prior allogeneic stem-cell transplantation (SCT)
- Completion of autologous SCT within 100 days prior to Day 1 of Cycle 1
- Prior standard or investigational anti-cancer therapy as specified: Radioimmunoconjugate within 12 weeks prior to Day 1 of Cycle 1; Monoclonal antibody 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
- Clinically significant toxicity (other than alopecia) from prior therapy that has not resolved to Grade less than or equal to (</=) 2 (according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0) prior to Day 1 of Cycle 1
- Grade 3b FL
- History of transformation of indolent disease to DLBCL (expansion-phase only)
- Central nervous system lymphoma or leptomeningeal infiltration
- Treatment with systemic corticosteroids >20 mg/day, prednisone or equivalent
- Clinical conditions requiring treatment with oral or parenteral anticoagulants or antiplatelet agents unless treatment can be discontinued 7 days (or 5 half-lives) prior to initiation of study treatment (except used as flushes for indwelling catheters)
- History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies
- Known hypersensitivity or allergy to murine products or any component of the obinutuzumab, rituximab, idasanutlin, or venetoclax formulation
- Current or history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or HCV antibody at screening
- History of progressive multifocal leukoencephalopathy (PML)
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results
- Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by study treatment, such as severe hereditary coagulation disorders or insulin-dependent diabetes mellitus that is not optimally controlled with medical management (example, presence of ketoacidosis)
- 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 study
- Inadequate hematologic function (unless due to underlying lymphoma), defined as follows: Hemoglobin less than (<) 9 grams per decilitre (g/dL), absolute neutrophil count (ANC) <1.5*10^9 cells per liter (cells/L), platelet count <75*10^9 cells/L
- Any of the following abnormal laboratory values (unless due to underlying lymphoma): International normalized ratio (INR) or prothrombin time (PT) >1.5*upper limit of normal (ULN) in the absence of therapeutic anticoagulation; partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) >1.5*ULN in the absence of a lupus anticoagulant
- Life expectancy <3 months
Sites / Locations
- University of Colorado
- The University of Chicago Medical Center
- Norton Cancer Institute - Dutchmans
- Mount Sinai Medical Center
- Allegheny General Hospital
- Guthrie Clinic
- Swedish Cancer Inst.
- Prince of Wales Hospital
- Westmead Hospital
- Linear Clinical Research Limited
- Klinikum Augsburg
- Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
- SLK-Kliniken Heilbronn GmbH
- Klinikum rechts der Isar der TU München
- Universitätsklinikum Würzburg; Studienzentrale Hämatologie/Onkologie
- Keimyung University Dongsan Medical Center
- Severance Hospital
- Asan Medical Center
- Samsung Medical Center
- Christchurch Hospital
- Auckland Clinical Studies Limited
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
Induction Treatment: Participants will receive either Regimen A or Regimen B. Regimen A: Participants will receive either obinutuzumab on Days 1, 8, 15 of Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin and venetoclax on Days 1 to 5 of Cycles 1 to 6 or obinutuzumab on Days 1, 8, 15 on Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin on Days 1 to 5 and venetoclax on Days 1 to 10 of Cycles 1 to 6. Regimen B (in bridging cohort): Participants will receive obinutuzumab alone in Cycle 1 and obinutuzumab with idasanutlin and venetoclax (both at maximum tolerated dose [MTD] established from Regimen A) in Cycles 2 to 6. Post-Induction Treatment (Maintenance Treatment): Participants will receive obinutuzumab every 2 months for 24 months; idasanutlin and venetoclax for 6 months.
Induction Treatment: Participants will receive either obinutuzumab on Days 1, 8, 15 of Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin and venetoclax on Days 1 to 5 of Cycles 1 to 6 or obinutuzumab on Days 1, 8, 15 on Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin on Days 1 to 5 and venetoclax on Days 1 to 10 of Cycles 1 to 6. In bridging cohort, participants will receive rituximab on Day 1 of Cycles 1 to 6 and idasanutlin and venetoclax (both at MTD) in Cycles 1 to 6. Post-Induction Treatment (Consolidation Treatment): Participants will receive obinutuzumab or rituximab (according to study treatment received in the induction) every 2 months for 6 months; idasanutlin and venetoclax for 6 months.
Induction Treatment: Participants will receive idasanutlin and venetoclax at the RP2D of the selected regimen (Regimen A or B) identified during the dose-escalation phase in combination with obinutuzumab. Regimen A: Participants will receive either obinutuzumab on Days 1, 8, 15 of Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin and venetoclax on Days 1 to 5 of Cycles 1 to 6 or obinutuzumab on Days 1, 8, 15 on Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin on Days 1 to 5 and venetoclax on Days 1 to 10 of Cycles 1 to 6. Regimen B (in bridging cohort): Participants will receive obinutuzumab alone in Cycle 1 and obinutuzumab with idasanutlin and venetoclax in Cycles 2 to 6. Post-Induction Treatment (Maintenance Treatment): Participants will receive obinutuzumab every 2 months for 24 months; idasanutlin and venetoclax for 6 months.
Induction Treatment: Participants will receive rituximab on Day 1 of Cycles 1 to 6; idasanutlin and venetoclax (both at RP2D) on Days 1 to 5 of Cycles 1 to 6 or rituximab on Day 1 of Cycles 1 to 6; idasanutlin on Days 1 to 5 and venetoclax on Days 1 to 10 of Cycles 1 to 6. Post-Induction Treatment (Consolidation Treatment): Participants will receive rituximab every 2 months for 6 months; idasanutlin and venetoclax for 6 months.
Outcomes
Primary Outcome Measures
RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab
It was planned to be identified in escalation and carried over in expansion phases. However the expansion phase did not take place. phases.
The study was closed because at escalation doses 100 (in combination with venetoclax 400 mg) and 150 mg (in combination with venetoclax 200 mg) Idasanutlin, the benefit was mild. The study was terminated at the escalation phase with DLTs showing AEs in all cohorts. The subpopulations of DLBCL and FL were showed no difference in their genetic subtype make-up, therefore, Cohorts Safety, 1, 2, 3 contain both populations.
The safety cohort had a different venetoclax schedule of 5 days to ensure safety. Remaining cohorts used a 10 days schedule. No RP2D was identified in the Cohorts 1 and 3.
RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab
It was planned to be identified in escalation and carried over in expansion phases. However the expansion phase did not take place.
The study was closed because at escalation doses 200 (in combination with 150 mg idasanutlin) and 400 (in combination with 100 mg idasanutlin) mg Venetoclax, the benefit was mild. The study was terminated at the escalation phase with DLTs showing AEs in all cohorts.
The safety cohort had a different venetoclax schedule of 5 days to ensure safety. Remaining cohorts used a 10 days schedule. No RP2D was identified in the Cohorts 1 and 3.
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
DLT is defined as any one of the following events occurring during first two Cycles of treatment and assessed by the investigator as clearly not related to patient's underlying disease: - Any Grade 5 adverse event (AE) unless unequivocally due to the underlying malignancy or extraneous causes; - AE of any grade that leads to a delay of more than 14 days at the start of next treatment cycle; - Hematologic AEs (neutropenia, thrombocytopenia); - Non-hematologic AE, except IRRs, laboratory TLS without manifestations of clinical TLS, AST or ALT, diarrhea, nausea or vomiting, fatigue, asthenia, anorexia, or constipation, hepatic transaminase.
Percentage of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a casual relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Percentage of Participants With Complete Response (CR), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography-Computed Tomography (PET-CT) Scans Using Modified Lugano 2014 Criteria
The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II), but the expansion phase was not opened (i.e., no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I). Therefore the result data not derived and not reported.
Secondary Outcome Measures
Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
The investigator evaluated responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT based complete response (CR), which required a complete metabolic response with a score of 1, 2 or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to [<=] mediastinum; 3 = uptake greater than [>] mediastinum and <= liver; 4 = uptake moderately > liver; 5 = uptake markedly > liver and/or new lesions). The CR criteria were slightly modified to require normal bone marrow by morphology (if intermediate, immunohistochemistry negative). PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were considered non-responders.
Percentage of Participants With CR, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required to complete radiologic response with all of the following: target nodal masses must regress to less than or equal to 1.5 centimeters in the longest transverse diameter of a lesion [LDi]; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunochemistry negative). CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders. Therefore the result data not derived and not reported.
Percentage of Participants With CR, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The investigator evaluated responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimeters in the longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). CT scans were performed at end of induction only on participants who received at least 2 cycles of Induction treatment; those without a post-baseline tumor assessment were to be considered non-responders. This outcome measure therefore not derived and not reported.
Percentage of Participants With Objective Response, Determined by the IRC on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
The IRC was to evaluate responses at the end of induction treatment using Luagno 2014 criteria for malignant lymphoma for a PET-CT based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2 or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 [no uptake above background] to 5 [uptake markedly higher than liver and/or new lesions]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Therefore the result data not derived and not reported. The study was pre-maturely terminated.
Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
The investigator was to evaluate responses at end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2, or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 [no uptake above background] to 5 [uptake markedly higher than liver and/or new lesions]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score of 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Participants without a post-baseline tumor assessment were to be considered non-responders.
Percentage of Participants With Objective Response, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a >=50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/nomal, regressed, but no increase; and spleen must have regressed by >50% in length. Therefore the result data not derived and not reported. The study was pre-maturely terminated.
Percentage of Participants With Objective Response at EOI, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a >=50% decrease in sum of the product of perpendicular diameters up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by >50% in length. The study was pre-maturely terminated at escalation phase.
Percentage of Participants With Objective Response During the Study, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a >=50% decrease in sum of the product of perpendicular diameters up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by >50% in length. The study was pre-maturely terminated at escalation phase.
Observed Serum Concentration of Obinutuzumab in Participants With FL
Observed Serum Concentration of Obinutuzumab in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Observed Serum Concentration of Obinutuzumab in Participants With DLBCL
Observed Serum Concentration of Obinutuzumab in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
Observed Serum Concentration of Rituximab in Participants With FL
Observed Serum Concentration of Rituximab in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
Observed Serum Concentration of Rituximab in Participants With DLBCL
Observed Serum Concentration of Rituximab in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
Observed Plasma Concentration of Idasanutlin in Participants With FL
Observed Plasma Concentration of Idasanutlin in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived therefore no result was reported
Observed Plasma Concentration of Idasanutlin in Participants With DLBCL
Observed Plasma Concentration of Idasanutlin in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived therefore no result was reported
Observed Plasma Concentration of Venetoclax in Participants With FL
Observed Plasma Concentration of Venetoclax in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated.
Observed Plasma Concentration of Venetoclax in Participants With DLBCL
Observed Plasma Concentration of Venetoclax in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03135262
Brief Title
A Study of Obinutuzumab in Combination With Idasanutlin and Venetoclax in Participants With Relapsed or Refractory (R/R) Follicular Lymphoma (FL) or Rituximab in Combination With Idasanutlin and Venetoclax in Participants With R/R Diffuse Large B-Cell Lymphoma (DLBCL)
Official Title
A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Idasanutlin and Venetoclax in Patients With Relapsed or Refractory Follicular Lymphoma and Obinutuzumab or Rituximab in Combination With Idasanutlin and Venetoclax in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
Sponsor's decision to terminate the study after Phase 1; will not proceed with Phase 2.
Study Start Date
June 15, 2017 (Actual)
Primary Completion Date
April 30, 2020 (Actual)
Study Completion Date
April 30, 2020 (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 Phase Ib/II, open-label, multicenter, non-randomized, dose-escalation study will evaluate the safety, efficacy, and pharmacokinetics of obinutuzumab in combination with idasanutlin and venetoclax in participants with R/R FL and obinutuzumab or rituximab in combination with idasanutlin and venetoclax in participants with R/R DLBCL. The study will include an initial dose-escalation phase followed by an expansion phase. The dose-escalation phase is designed to determine the recommended phase II doses (RP2Ds) and regimen for idasanutlin and venetoclax in combination with obinutuzumab for FL participants and in combination with rituximab for DLBCL participants.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma, Lymphoma, Large B-Cell, Diffuse
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
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose-Escalation Cohort: FL
Arm Type
Experimental
Arm Description
Induction Treatment: Participants will receive either Regimen A or Regimen B. Regimen A: Participants will receive either obinutuzumab on Days 1, 8, 15 of Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin and venetoclax on Days 1 to 5 of Cycles 1 to 6 or obinutuzumab on Days 1, 8, 15 on Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin on Days 1 to 5 and venetoclax on Days 1 to 10 of Cycles 1 to 6. Regimen B (in bridging cohort): Participants will receive obinutuzumab alone in Cycle 1 and obinutuzumab with idasanutlin and venetoclax (both at maximum tolerated dose [MTD] established from Regimen A) in Cycles 2 to 6. Post-Induction Treatment (Maintenance Treatment): Participants will receive obinutuzumab every 2 months for 24 months; idasanutlin and venetoclax for 6 months.
Arm Title
Dose-Escalation Cohort: DLBCL
Arm Type
Experimental
Arm Description
Induction Treatment: Participants will receive either obinutuzumab on Days 1, 8, 15 of Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin and venetoclax on Days 1 to 5 of Cycles 1 to 6 or obinutuzumab on Days 1, 8, 15 on Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin on Days 1 to 5 and venetoclax on Days 1 to 10 of Cycles 1 to 6. In bridging cohort, participants will receive rituximab on Day 1 of Cycles 1 to 6 and idasanutlin and venetoclax (both at MTD) in Cycles 1 to 6. Post-Induction Treatment (Consolidation Treatment): Participants will receive obinutuzumab or rituximab (according to study treatment received in the induction) every 2 months for 6 months; idasanutlin and venetoclax for 6 months.
Arm Title
Expansion Cohort: FL
Arm Type
Experimental
Arm Description
Induction Treatment: Participants will receive idasanutlin and venetoclax at the RP2D of the selected regimen (Regimen A or B) identified during the dose-escalation phase in combination with obinutuzumab. Regimen A: Participants will receive either obinutuzumab on Days 1, 8, 15 of Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin and venetoclax on Days 1 to 5 of Cycles 1 to 6 or obinutuzumab on Days 1, 8, 15 on Cycle 1 and then on Day 1 of Cycles 2 to 6; idasanutlin on Days 1 to 5 and venetoclax on Days 1 to 10 of Cycles 1 to 6. Regimen B (in bridging cohort): Participants will receive obinutuzumab alone in Cycle 1 and obinutuzumab with idasanutlin and venetoclax in Cycles 2 to 6. Post-Induction Treatment (Maintenance Treatment): Participants will receive obinutuzumab every 2 months for 24 months; idasanutlin and venetoclax for 6 months.
Arm Title
Expansion Cohort: DLBCL
Arm Type
Experimental
Arm Description
Induction Treatment: Participants will receive rituximab on Day 1 of Cycles 1 to 6; idasanutlin and venetoclax (both at RP2D) on Days 1 to 5 of Cycles 1 to 6 or rituximab on Day 1 of Cycles 1 to 6; idasanutlin on Days 1 to 5 and venetoclax on Days 1 to 10 of Cycles 1 to 6. Post-Induction Treatment (Consolidation Treatment): Participants will receive rituximab every 2 months for 6 months; idasanutlin and venetoclax for 6 months.
Intervention Type
Drug
Intervention Name(s)
Idasanutlin
Intervention Description
Induction Treatment: Idasanutlin tablets will be administered orally once daily at escalated doses (starting dose 100 milligrams [mg], maximum 600 mg). Post-Induction Treatment: The dose and regimen will be determined by the Sponsor after review of all relevant data. The dose for maintenance/consolidation will not exceed the dose the participant received during induction.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
Participants will receive a fixed dose of obinutuzumab, 1000 mg by intravenous (IV) infusion on Days 1, 8 and 15 of Cycle 1 and on Day 1 of each subsequent cycle (Cycles 2 to 6) (each cycle = 28 days) during induction treatment, and on Day 1 of every other month during maintenance treatment (eligible participants with FL only) or during consolidation treatment (eligible participants with DLBCL only).
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Intervention Description
Induction Treatment: Venetoclax tablets will be administered orally once daily at escalated doses (starting dose 200 mg, maximum 800 mg). Post-Induction Treatment: The dose and regimen will be determined by the Sponsor after review of all relevant data. The dose for maintenance/consolidation will not exceed the dose the participant received during induction.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab will be administered by IV infusion at a dose of 375 milligrams per square meter (mg/m^2) on Day 1 of Cycles 1-6 during induction treatment and on Day 1 of every other month during consolidation treatment.
Primary Outcome Measure Information:
Title
RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab
Description
It was planned to be identified in escalation and carried over in expansion phases. However the expansion phase did not take place. phases.
The study was closed because at escalation doses 100 (in combination with venetoclax 400 mg) and 150 mg (in combination with venetoclax 200 mg) Idasanutlin, the benefit was mild. The study was terminated at the escalation phase with DLTs showing AEs in all cohorts. The subpopulations of DLBCL and FL were showed no difference in their genetic subtype make-up, therefore, Cohorts Safety, 1, 2, 3 contain both populations.
The safety cohort had a different venetoclax schedule of 5 days to ensure safety. Remaining cohorts used a 10 days schedule. No RP2D was identified in the Cohorts 1 and 3.
Time Frame
Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days)
Title
RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab
Description
It was planned to be identified in escalation and carried over in expansion phases. However the expansion phase did not take place.
The study was closed because at escalation doses 200 (in combination with 150 mg idasanutlin) and 400 (in combination with 100 mg idasanutlin) mg Venetoclax, the benefit was mild. The study was terminated at the escalation phase with DLTs showing AEs in all cohorts.
The safety cohort had a different venetoclax schedule of 5 days to ensure safety. Remaining cohorts used a 10 days schedule. No RP2D was identified in the Cohorts 1 and 3.
Time Frame
Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days)
Title
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Description
DLT is defined as any one of the following events occurring during first two Cycles of treatment and assessed by the investigator as clearly not related to patient's underlying disease: - Any Grade 5 adverse event (AE) unless unequivocally due to the underlying malignancy or extraneous causes; - AE of any grade that leads to a delay of more than 14 days at the start of next treatment cycle; - Hematologic AEs (neutropenia, thrombocytopenia); - Non-hematologic AE, except IRRs, laboratory TLS without manifestations of clinical TLS, AST or ALT, diarrhea, nausea or vomiting, fatigue, asthenia, anorexia, or constipation, hepatic transaminase.
Time Frame
Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days)
Title
Percentage of Participants With Adverse Events (AEs)
Description
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a casual relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame
From Baseline up to approximately 48 months
Title
Percentage of Participants With Complete Response (CR), Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography-Computed Tomography (PET-CT) Scans Using Modified Lugano 2014 Criteria
Description
The study plan was for the IRC to analyze the efficacy results in participants from the expansion phase (Part II), but the expansion phase was not opened (i.e., no enrollment) because the sponsor decided to terminate the study early due to the modest benefit achieved with the maximum tolerated dose during the dose escalation phase (Part I). Therefore the result data not derived and not reported.
Time Frame
At end of Induction (EOI) (within 6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days])
Secondary Outcome Measure Information:
Title
Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
Description
The investigator evaluated responses at the end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT based complete response (CR), which required a complete metabolic response with a score of 1, 2 or 3 with or without a residual mass in lymph nodes and extralymphatic sites on the PET 5-point scale for 18-fluorodeoxyglucose (FDG) uptake (1 = no uptake above background; 2 = uptake less than or equal to [<=] mediastinum; 3 = uptake greater than [>] mediastinum and <= liver; 4 = uptake moderately > liver; 5 = uptake markedly > liver and/or new lesions). The CR criteria were slightly modified to require normal bone marrow by morphology (if intermediate, immunohistochemistry negative). PET-CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were considered non-responders.
Time Frame
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Title
Percentage of Participants With CR, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
Description
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required to complete radiologic response with all of the following: target nodal masses must regress to less than or equal to 1.5 centimeters in the longest transverse diameter of a lesion [LDi]; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunochemistry negative). CT scans were performed at end of induction only on participants who had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders. Therefore the result data not derived and not reported.
Time Frame
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Title
Percentage of Participants With CR, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
Description
The investigator evaluated responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a computed tomography (CT)-based complete response (CR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimeters in the longest transverse diameter of a lesion (LDi); no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). CT scans were performed at end of induction only on participants who received at least 2 cycles of Induction treatment; those without a post-baseline tumor assessment were to be considered non-responders. This outcome measure therefore not derived and not reported.
Time Frame
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Title
Percentage of Participants With Objective Response, Determined by the IRC on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
Description
The IRC was to evaluate responses at the end of induction treatment using Luagno 2014 criteria for malignant lymphoma for a PET-CT based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2 or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 [no uptake above background] to 5 [uptake markedly higher than liver and/or new lesions]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Therefore the result data not derived and not reported. The study was pre-maturely terminated.
Time Frame
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Title
Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
Description
The investigator was to evaluate responses at end of induction treatment using Lugano 2014 criteria for malignant lymphoma for a PET-CT based objective response: either a complete (CR) or partial response (PR). A CR required a complete metabolic response with a score of 1, 2, or 3 on the PET 5-point scale (5PS) for 18-fluorodeoxyglucose (FDG) uptake (scores range from 1 [no uptake above background] to 5 [uptake markedly higher than liver and/or new lesions]), with or without a residual mass in lymph nodes and extralymphatic sites; and a PR required a partial metabolic response with a score of 4 or 5 on the 5PS with reduced 18-FDG uptake compared with baseline and residual mass(es) of any size. For bone marrow involvement, the CR criteria required no evidence of FDG-avid disease, and the PR criteria required residual uptake higher than in normal marrow but reduced compared with baseline. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time Frame
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Title
Percentage of Participants With Objective Response, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
Description
The IRC was to evaluate responses at the end of induction treatment using the Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in the LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a >=50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/nomal, regressed, but no increase; and spleen must have regressed by >50% in length. Therefore the result data not derived and not reported. The study was pre-maturely terminated.
Time Frame
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Title
Percentage of Participants With Objective Response at EOI, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
Description
The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a >=50% decrease in sum of the product of perpendicular diameters up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by >50% in length. The study was pre-maturely terminated at escalation phase.
Time Frame
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
Title
Percentage of Participants With Objective Response During the Study, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
Description
The investigator was to evaluate responses at the end of induction treatment using Lugano 2014 response criteria for malignant lymphoma for a CT-based objective response: either a complete (CR) or partial response (PR). The CR criteria required a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 cm in LDi; no extralymphatic sites of disease; no non-measured or new lesions; enlarged organs regressing to normal size; and bone marrow normal by morphology (if indeterminate, immunohistochemistry negative). The PR criteria required all of the following: a >=50% decrease in sum of the product of perpendicular diameters up to 6 target measurable nodes and extranodal sites; no new lesions; non-measured lesion that is absent/normal, regressed, but no increase; and spleen must have regressed by >50% in length. The study was pre-maturely terminated at escalation phase.
Time Frame
From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months
Title
Observed Serum Concentration of Obinutuzumab in Participants With FL
Description
Observed Serum Concentration of Obinutuzumab in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
Time Frame
From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months (detailed timeframe is mentioned in outcome measure description)
Title
Observed Serum Concentration of Obinutuzumab in Participants With DLBCL
Description
Observed Serum Concentration of Obinutuzumab in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
Time Frame
Induction: Pre-dose (any time prior to dose on same day) and 30 min post-dose on Day 1 of Cycle 1; Pre-dose (within 5 hrs prior to dose) and 30 min post-dose on Day 1 of Cycles 2, 4 and 6 (each cycle = 28 days)
Title
Observed Serum Concentration of Rituximab in Participants With FL
Description
Observed Serum Concentration of Rituximab in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
Time Frame
Induction: Pre-dose (any time prior to dose on same day) on Day 1 of Cycle 1; Pre-dose (within 5 hrs prior to dose) on Day 1 of Cycles 2, 4, 6; 30 min post-dose on Day 1 of Cycles 1 and 6 (each cycle = 28 days)
Title
Observed Serum Concentration of Rituximab in Participants With DLBCL
Description
Observed Serum Concentration of Rituximab in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived, therefore no result was reported.
Time Frame
From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months (detailed timeframe is mentioned in outcome measure description)
Title
Observed Plasma Concentration of Idasanutlin in Participants With FL
Description
Observed Plasma Concentration of Idasanutlin in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived therefore no result was reported
Time Frame
From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description)
Title
Observed Plasma Concentration of Idasanutlin in Participants With DLBCL
Description
Observed Plasma Concentration of Idasanutlin in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated. No result data was derived therefore no result was reported
Time Frame
From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description)
Title
Observed Plasma Concentration of Venetoclax in Participants With FL
Description
Observed Plasma Concentration of Venetoclax in Participants With FL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated.
Time Frame
From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description)
Title
Observed Plasma Concentration of Venetoclax in Participants With DLBCL
Description
Observed Plasma Concentration of Venetoclax in Participants With DLBCL was planned to be determined as part of the pharmacokinetics analyses during the expansion phase which did not take place.
The study was prematurely terminated because of the overall modest benefit achieved with MTD during the escalation phase (Part 1); Phase II of the study (expansion) was never initiated.
Time Frame
From Day 1 of Cycle 1 up to Day 5 of Cycle 4 (each cycle = 28 days) (detailed timeframe is mentioned in outcome measure description)
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
B-cell lymphoma classified as either of the following: R/R FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-cluster of differentiation 20 (CD20) monoclonal antibody; R/R DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody in participants who are not eligible for second line combination chemotherapy and autologous stem-cell transplantation, have failed second line combination chemotherapy, or experienced disease progression following autologous stem-cell transplantation
Histologically documented CD20-positive lymphoma
Fluorodeoxyglucose (FDG)-avid lymphoma (that is [i.e.], PET-positive lymphoma)
At least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension by CT scan or magnetic resonance imaging [MRI])
Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL
Exclusion Criteria:
Known CD20-negative status at relapse or progression
Prior allogeneic stem-cell transplantation (SCT)
Completion of autologous SCT within 100 days prior to Day 1 of Cycle 1
Prior standard or investigational anti-cancer therapy as specified: Radioimmunoconjugate within 12 weeks prior to Day 1 of Cycle 1; Monoclonal antibody 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
Clinically significant toxicity (other than alopecia) from prior therapy that has not resolved to Grade less than or equal to (</=) 2 (according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0) prior to Day 1 of Cycle 1
Grade 3b FL
History of transformation of indolent disease to DLBCL (expansion-phase only)
Central nervous system lymphoma or leptomeningeal infiltration
Treatment with systemic corticosteroids >20 mg/day, prednisone or equivalent
Clinical conditions requiring treatment with oral or parenteral anticoagulants or antiplatelet agents unless treatment can be discontinued 7 days (or 5 half-lives) prior to initiation of study treatment (except used as flushes for indwelling catheters)
History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies
Known hypersensitivity or allergy to murine products or any component of the obinutuzumab, rituximab, idasanutlin, or venetoclax formulation
Current or history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or HCV antibody at screening
History of progressive multifocal leukoencephalopathy (PML)
History of other malignancy that could affect compliance with the protocol or interpretation of results
Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results
Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by study treatment, such as severe hereditary coagulation disorders or insulin-dependent diabetes mellitus that is not optimally controlled with medical management (example, presence of ketoacidosis)
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 study
Inadequate hematologic function (unless due to underlying lymphoma), defined as follows: Hemoglobin less than (<) 9 grams per decilitre (g/dL), absolute neutrophil count (ANC) <1.5*10^9 cells per liter (cells/L), platelet count <75*10^9 cells/L
Any of the following abnormal laboratory values (unless due to underlying lymphoma): International normalized ratio (INR) or prothrombin time (PT) >1.5*upper limit of normal (ULN) in the absence of therapeutic anticoagulation; partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) >1.5*ULN in the absence of a lupus anticoagulant
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 Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045-2517
Country
United States
Facility Name
The University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Norton Cancer Institute - Dutchmans
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Allegheny General Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Guthrie Clinic
City
Sayre
State/Province
Pennsylvania
ZIP/Postal Code
18840
Country
United States
Facility Name
Swedish Cancer Inst.
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Prince of Wales Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Linear Clinical Research Limited
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Klinikum Augsburg
City
Augsburg
ZIP/Postal Code
86156
Country
Germany
Facility Name
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
SLK-Kliniken Heilbronn GmbH
City
Heilbronn
ZIP/Postal Code
74078
Country
Germany
Facility Name
Klinikum rechts der Isar der TU München
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Universitätsklinikum Würzburg; Studienzentrale Hämatologie/Onkologie
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Keimyung University Dongsan Medical Center
City
Daegu
ZIP/Postal Code
41931
Country
Korea, Republic of
Facility Name
Severance Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
Facility Name
Auckland Clinical Studies Limited
City
Grafton
ZIP/Postal Code
1010
Country
New Zealand
12. IPD Sharing Statement
Learn more about this trial
A Study of Obinutuzumab in Combination With Idasanutlin and Venetoclax in Participants With Relapsed or Refractory (R/R) Follicular Lymphoma (FL) or Rituximab in Combination With Idasanutlin and Venetoclax in Participants With R/R Diffuse Large B-Cell Lymphoma (DLBCL)
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