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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03135262
Registration number
NCT03135262
Ethics application status
Date submitted
26/04/2017
Date registered
1/05/2017
Date last updated
7/12/2021
Titles & IDs
Public 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)
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Scientific 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
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Secondary ID [1]
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2016-002480-34
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Secondary ID [2]
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BH39147
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Follicular Lymphoma
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Lymphoma, Large B-Cell, Diffuse
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Condition category
Condition code
Cancer
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Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
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Cancer
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Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Idasanutlin
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Venetoclax
Treatment: Drugs - Rituximab
Experimental: Dose-Escalation Cohort: FL - 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.
Experimental: Dose-Escalation Cohort: DLBCL - 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.
Experimental: Expansion Cohort: FL - 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.
Experimental: Expansion Cohort: DLBCL - 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.
Treatment: Drugs: Idasanutlin
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.
Treatment: Drugs: Obinutuzumab
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).
Treatment: Drugs: Venetoclax
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.
Treatment: Drugs: Rituximab
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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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RP2D of Idasanutlin When Given in Combination With Obinutuzumab or Rituximab
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Assessment method [1]
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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.
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Timepoint [1]
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Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days)
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Primary outcome [2]
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RP2D of Venetoclax When Given in Combination With Obinutuzumab or Rituximab
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Assessment method [2]
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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.
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Timepoint [2]
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Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days)
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Primary outcome [3]
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Percentage of Participants With Dose-Limiting Toxicities (DLTs)
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Assessment method [3]
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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.
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Timepoint [3]
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Cycle 1 Day 1 up to Cycle 2 Day 28 (each cycle = 28 days)
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Primary outcome [4]
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Percentage of Participants With Adverse Events (AEs)
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Assessment method [4]
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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.
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Timepoint [4]
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From Baseline up to approximately 48 months
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Primary outcome [5]
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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
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Assessment method [5]
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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.
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Timepoint [5]
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At end of Induction (EOI) (within 6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days])
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Secondary outcome [1]
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Percentage of Participants With CR, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
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Assessment method [1]
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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.
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Timepoint [1]
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At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
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Secondary outcome [2]
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Percentage of Participants With CR, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
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Assessment method [2]
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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.
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Timepoint [2]
0
0
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
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Secondary outcome [3]
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Percentage of Participants With CR, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
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Assessment method [3]
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0
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.
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Timepoint [3]
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0
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
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Secondary outcome [4]
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Percentage of Participants With Objective Response, Determined by the IRC on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
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Assessment method [4]
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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.
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Timepoint [4]
0
0
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
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Secondary outcome [5]
0
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Percentage of Participants With Objective Response, Determined by the Investigator on the Basis of PET-CT Scans Using Modified Lugano 2014 Criteria
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Assessment method [5]
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0
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.
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Timepoint [5]
0
0
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
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Secondary outcome [6]
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Percentage of Participants With Objective Response, Determined by the IRC on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
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Assessment method [6]
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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.
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Timepoint [6]
0
0
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
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Secondary outcome [7]
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Percentage of Participants With Objective Response at EOI, Determined by the Investigator on the Basis of CT Scans Alone Using Modified Lugano 2014 Criteria
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Assessment method [7]
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0
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.
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Timepoint [7]
0
0
At EOI (6 to 8 weeks after Cycle 6 Day 1 [up to approximately 28 weeks] [each cycle = 28 days]
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Secondary outcome [8]
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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
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Assessment method [8]
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0
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.
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Timepoint [8]
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0
From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months
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Secondary outcome [9]
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Observed Serum Concentration of Obinutuzumab in Participants With FL
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Assessment method [9]
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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.
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Timepoint [9]
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0
From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months (detailed timeframe is mentioned in outcome measure description)
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Secondary outcome [10]
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Observed Serum Concentration of Obinutuzumab in Participants With DLBCL
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Assessment method [10]
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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.
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Timepoint [10]
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0
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)
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Secondary outcome [11]
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Observed Serum Concentration of Rituximab in Participants With FL
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Assessment method [11]
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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.
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Timepoint [11]
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0
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)
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Secondary outcome [12]
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Observed Serum Concentration of Rituximab in Participants With DLBCL
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Assessment method [12]
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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.
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Timepoint [12]
0
0
From Day 1 of Cycle 1 (cycle length = 28 days) up to approximately 48 months (detailed timeframe is mentioned in outcome measure description)
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Secondary outcome [13]
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Observed Plasma Concentration of Idasanutlin in Participants With FL
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Assessment method [13]
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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
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Timepoint [13]
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0
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)
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Secondary outcome [14]
0
0
Observed Plasma Concentration of Idasanutlin in Participants With DLBCL
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Assessment method [14]
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0
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
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Timepoint [14]
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0
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)
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Secondary outcome [15]
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0
Observed Plasma Concentration of Venetoclax in Participants With FL
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Assessment method [15]
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0
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.
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Timepoint [15]
0
0
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)
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Secondary outcome [16]
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0
Observed Plasma Concentration of Venetoclax in Participants With DLBCL
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Assessment method [16]
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0
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.
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Timepoint [16]
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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)
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Eligibility
Key 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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
15/06/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
30/04/2020
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Sample size
Target
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Accrual to date
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Final
29
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Recruitment in Australia
Recruitment state(s)
NSW,WA
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Recruitment hospital [1]
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0
Prince of Wales Hospital - Randwick
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Recruitment hospital [2]
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Westmead Hospital - Westmead
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Recruitment hospital [3]
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Linear Clinical Research Limited - Nedlands
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Recruitment postcode(s) [1]
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2031 - Randwick
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Recruitment postcode(s) [2]
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2145 - Westmead
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Recruitment postcode(s) [3]
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6009 - Nedlands
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Recruitment outside Australia
Country [1]
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0
United States of America
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State/province [1]
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Colorado
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Country [2]
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0
United States of America
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State/province [2]
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0
Illinois
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Country [3]
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0
United States of America
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State/province [3]
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Kentucky
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Country [4]
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United States of America
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State/province [4]
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New York
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Country [5]
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0
United States of America
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State/province [5]
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Pennsylvania
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Country [6]
0
0
United States of America
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State/province [6]
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0
Washington
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Country [7]
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0
Germany
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State/province [7]
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Augsburg
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Country [8]
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Germany
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State/province [8]
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Dresden
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Country [9]
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Germany
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State/province [9]
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Heilbronn
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Country [10]
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Germany
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State/province [10]
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München
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Country [11]
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Germany
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State/province [11]
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Würzburg
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Country [12]
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Korea, Republic of
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State/province [12]
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Daegu
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Country [13]
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Korea, Republic of
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State/province [13]
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Seoul
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Country [14]
0
0
New Zealand
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State/province [14]
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Christchurch
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Country [15]
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New Zealand
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State/province [15]
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0
Grafton
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Hoffmann-La Roche
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03135262
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Clinical Trials
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Address
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Hoffmann-La Roche
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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0
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Country
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0
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Phone
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0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03135262
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