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A Study of Idasanutlin in Combination With Obinutuzumab in Relapsed/Refractory (R/R) Follicular Lymphoma (FL) and in Combination With Rituximab in R/R Diffuse Large B-Cell Lymphoma (DLBCL) Participants

Primary Purpose

Non-Hodgkin's Lymphoma

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Idasanutlin
Obinutuzumab
Rituximab
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

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

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Histologically documented cluster of differentiation (CD) 20-positive B-cell lymphoma classified as relapsed or refractory FL or DLBCL after treatment with at least two prior chemoimmunotherapy regimens that included an anti-CD20 monoclonal antibody (mAb) and for which no other more appropriate treatment option exists
  • At least one bidimensionally measurable lesion
  • Agreement to remain abstinent or use adequate contraception, among women or men of childbearing potential

Exclusion Criteria:

  • Known CD20-negative status at relapse or progression
  • Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1
  • Current use of systemic corticosteroids greater than (>) 20 mg prednisone per day (or equivalent), or prior anti-cancer therapy to include: radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1
  • Requirement for chronic anticoagulation
  • Central nervous system (CNS) disease
  • Active infection
  • Positive for human immunodeficiency virus (HIV) or hepatitis B or C
  • Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1
  • Poor hematologic, renal, or hepatic function
  • Pregnant or lactating women
  • History of progressive multifocal leukoencephalopathy (PML)

Sites / Locations

  • Mayo Clinic Arizona
  • University of Colorado
  • Norton Medical Plaza II
  • Swedish Cancer Institute
  • Western Pennsylvania Hospital
  • Guthrie Clinic
  • Rhode Island Hospital
  • Virginia Commonwealth University
  • Prince of Wales Hospital
  • Westmead Hospital
  • Linear Clinical Research Limited
  • Zentralklinikum Augsburg
  • Charité Research Organisation GmbH Campus-Virchow-Klinikum
  • SLK-Kliniken Heilbronn GmbH
  • Universitätsklinikum Köln
  • Universitätsklinikum Wurzburg
  • Keimyung University Dongsan Medical Center
  • National Cancer Center
  • Severance Hospital, Yonsei University Health System
  • Asan Medical Center
  • Samsung Medical Center
  • North Shore Hospital
  • Christchurch Hospital
  • Auckland Clinical Studies Limited

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg

DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg

DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg

DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2

DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2

FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg

FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg

FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg

Arm Description

Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 100 milligrams (mg) orally in combination with a fixed dose of obinutuzumab 1000 mg intravenously (IV) for 6 cycles (1 cycle = 28 days).

Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).

Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 200 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).

Participants with diffuse large B-cell lymphoma (DLBCL) in this bridging cohort received induction treatment with idasanutlin 150 mg orally in combination with rituximab 375 milligrams per square meter of body surface area (mg/m^2) IV for 6 cycles (1 cycle = 28 days).

Participants with diffuse large B-cell lymphoma (DLBCL) in this bridging cohort received induction treatment with idasanutlin 200 mg orally in combination with rituximab 375 mg/m^2 IV for 6 cycles (1 cycle = 28 days).

Participants with follicular lymphoma (FL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 100 milligrams (mg) orally in combination with a fixed dose of obinutuzumab 1000 mg intravenously (IV) for 6 cycles (1 cycle = 28 days).

Participants with follicular lymphoma (FL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).

Participants with follicular lymphoma (FL) in this bridging cohort received induction treatment with single-agent obinutuzumab 1000 mg IV for Cycle 1 and then idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for Cycles 2-6 (1 cycle = 28 days).

Outcomes

Primary Outcome Measures

Percentage of Participants With Complete Response at the End of Induction, Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scans Using Modified Lugano 2014 Criteria
The plan was for the IRC to evaluate responses at the end of induction treatment in participants from the expansion phase 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 indeterminate, 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 to be considered non-responders.

Secondary Outcome Measures

Number of Participants With a Dose-Limiting Toxicity
A dose-limiting toxicity (DLT) was defined as at least one of the following events occurring during Cycle 1 (or first 2 cycles in the bridging FL cohort) of treatment and assessed by the investigator as not clearly related to the underlying disease: Any Grade 5 adverse event (AE; severity graded per NCI-CTCAE v4.0) unless due to the underlying malignancy or extraneous causes; AE of any grade that leads to a delay of more than (>)14 days in the start of the next treatment cycle; Grade 3 or 4 non-hematologic AEs (with exceptions); Lab results suggestive of potential drug-induced liver injury (according to Hy's law); Grade 3 or 4 neutropenia in the presence of sustained fever of >38 C (lasting >5 days) or a documented infection; Grade 4 neutropenia or thrombocytopenia lasting >7 days; Grade 3 or 4 thrombocytopenia if associated with Grade ≥3 bleeding; Other toxicities considered clinically relevant and related to study treatment as determined by the investigator and medical monitor.
Percentage of Participants With Complete Response at the End of Induction, 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 indeterminate, 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 Complete Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using 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; X = new areas of uptake unlikely to be related to lymphoma). The CR criteria for participants with bone marrow involvement at screening required no evidence of FDG-avid disease in the marrow. 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 Complete Response at the End of Induction, Determined by the IRC on the Basis of CT Scans Alone Using 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 a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimetres 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 had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of CT Scans Alone Using 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 centimetres 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 had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
Percentage of Participants With Objective Response at the End of Induction, Determined by the IRC on the Basis of PET-CT Scans Using Lugano 2014 Criteria
The IRC was to evaluate responses at the 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 at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Lugano 2014 Criteria
The investigator was to evaluate responses at the 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 at the End of Induction, Determined by an IRC on the Basis of CT Scans Alone Using 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/normal, regressed, but no increase; and spleen must have regressed by >50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
Percentage of Participants With Objective Response at the End of Induction, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
The investigator 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/normal, regressed, but no increase; and spleen must have regressed by >50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
Percentage of Participants With Best Response of Complete Response or Partial Response During the Study, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
The investigator was to evaluate responses throughout the study using the Lugano 2014 response criteria for malignant lymphoma for a CT-based best response of 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/normal, regressed, but no increase; and spleen must have regressed by >50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
Plasma Idasanutlin Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints Grouped by Idasanutlin Dose and Combination Partner (Obinutuzumab or Rituximab)
The concentration of idasanutlin was determined using a validated assay. The duplication of the predose timepoint (0 hours) on Day 5 as an additional 24-hour timepoint on Day 5 was done in order to conduct pharmacokinetics analysis via non-compartmental analysis, and to derive idasanutlin exposure estimates up to the 24-hour post Day 5 dosing.
Serum Obinutuzumab Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints
Serum Rituximab Concentrations in DLBCL Participants at Nominal Sampling Timepoints
Safety Summary of the Number of Participants With at Least One Adverse Event by Type and Severity According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)
The adverse event (AE) severity grading scale for the NCI CTCAE v4.0 was used for assessing AE severity. Any AEs that were not specifically listed in the NCI CTCAE, v4.0 were graded per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Baseline Value and Change From Baseline Values of Systolic Blood Pressure at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Baseline Value and Change From Baseline Values of Diastolic Blood Pressure at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Baseline Value and Change From Baseline Values of Pulse Rate at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Baseline Value and Change From Baseline Values of Respiratory Rate at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Baseline Value and Change From Baseline Values of Body Temperature at Specified Timepoints
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Number of Participants by Electrocardiogram (ECG) Results Assessment Shift From Baseline to Specified Post-Baseline Timepoints
Single, resting, 12-lead ECG recordings were to be obtained after the participant had been resting in a supine position for at least 10 minutes. Any morphologic waveform changes or other ECG abnormalities were to be documented and clinical significance was determined based on the presence of symptoms, per the investigator's judgment. If the ECG assessment was missing at baseline then it was recorded as "Missing". The ECG results assessments are presented as the shift from baseline to post-baseline assessments at each timepoint. BL = baseline; Cyc1, D1 = Induction Cycle 1 Day 1; Cyc4, D1 = Induction Cycle 4 Day 1; CS = Clinically Significant; EOI = End of Induction Treatment - Completion/Discontinuation; EOM = End of Maintenance Treatment - Completion/Discontinuation; MM1 = Maintenance Month 1; Unsched = Unscheduled Visit
Hematology Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
Clinical laboratory tests for hematology parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) at baseline to the highest grade post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a patient with multiple post-baseline abnormalities, the highest (worst) grade for a given lab test is reported. Abs. = absolute count; BL = baseline; WBC = white blood cell count
Blood Chemistry Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
Clinical laboratory tests for blood chemistry parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) at baseline to the highest grade post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a patient with multiple post-baseline abnormalities, the highest (worst) grade for a given lab test is reported. BL = Baseline; Blood Gluc., Fast. = blood glucose, fasting; SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase; SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase; Triacylglyc. Lipase = triacylglycerol lipase

Full Information

First Posted
December 1, 2015
Last Updated
April 29, 2020
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02624986
Brief Title
A Study of Idasanutlin in Combination With Obinutuzumab in Relapsed/Refractory (R/R) Follicular Lymphoma (FL) and in Combination With Rituximab in R/R Diffuse Large B-Cell Lymphoma (DLBCL) Participants
Official Title
A Phase Ib/II Study Evaluating the Safety and Efficacy of Obinutuzumab in Combination With Idasanutlin in Patients With Relapsed or Refractory Follicular Lymphoma and Obinutuzumab or Rituximab in Combination With Idasanutlin in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
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
December 23, 2015 (Actual)
Primary Completion Date
May 20, 2019 (Actual)
Study Completion Date
May 20, 2019 (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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a open-label, multicenter, non-randomized, study to evaluate the safety, efficacy, and pharmacokinetics of idasanutlin in combination with obinutuzumab in participants with R/R FL and rituximab in combination with idasanutlin in 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 2 dose (RP2D) for idasanutlin in combination with obinutuzumab for FL and in combination with rituximab for DLBCL. The expansion phase is designed to further assess the safety and efficacy of obinutuzumab in combination with idasanutlin at the RP2D with the selected regimen in participants with R/R FL and of rituximab in combination with idasanutlin at the RP2D in participants with R/R DLBCL.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
DLBCL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg
Arm Type
Experimental
Arm Description
Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 100 milligrams (mg) orally in combination with a fixed dose of obinutuzumab 1000 mg intravenously (IV) for 6 cycles (1 cycle = 28 days).
Arm Title
DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg
Arm Type
Experimental
Arm Description
Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).
Arm Title
DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg
Arm Type
Experimental
Arm Description
Participants with diffuse large B-cell lymphoma (DLBCL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 200 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).
Arm Title
DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2
Arm Type
Experimental
Arm Description
Participants with diffuse large B-cell lymphoma (DLBCL) in this bridging cohort received induction treatment with idasanutlin 150 mg orally in combination with rituximab 375 milligrams per square meter of body surface area (mg/m^2) IV for 6 cycles (1 cycle = 28 days).
Arm Title
DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2
Arm Type
Experimental
Arm Description
Participants with diffuse large B-cell lymphoma (DLBCL) in this bridging cohort received induction treatment with idasanutlin 200 mg orally in combination with rituximab 375 mg/m^2 IV for 6 cycles (1 cycle = 28 days).
Arm Title
FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg
Arm Type
Experimental
Arm Description
Participants with follicular lymphoma (FL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 100 milligrams (mg) orally in combination with a fixed dose of obinutuzumab 1000 mg intravenously (IV) for 6 cycles (1 cycle = 28 days).
Arm Title
FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg
Arm Type
Experimental
Arm Description
Participants with follicular lymphoma (FL) in this non-bridging dose-escalation cohort received induction treatment with idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for 6 cycles (1 cycle = 28 days).
Arm Title
FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg
Arm Type
Experimental
Arm Description
Participants with follicular lymphoma (FL) in this bridging cohort received induction treatment with single-agent obinutuzumab 1000 mg IV for Cycle 1 and then idasanutlin 150 mg orally in combination with a fixed dose of obinutuzumab 1000 mg IV for Cycles 2-6 (1 cycle = 28 days).
Intervention Type
Drug
Intervention Name(s)
Idasanutlin
Other Intervention Name(s)
RO5503781
Intervention Description
Participants received idasanutlin film-coated tablets orally at a starting dose of 100 mg daily on Days 1 to 5 of each 28-day cycle. Escalation was to occur in at least 50-mg increments, and daily doses greater than or equal to (≥) 400 mg will be split into twice daily dosing.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Other Intervention Name(s)
RO5072759
Intervention Description
Participants received a fixed dose of obinutuzumab 1000 mg intravenous (IV) infusion to be given on Days 1, 8 and 15 of Cycle 1 and on Day 1 of Cycles 2 to 6 (1 cycle = 28 days). For eligible participants with FL, post-induction treatment was to be given at a dose of 1000 mg via IV infusion on Day 1 once every 2 months for a maximum of up to 24 months.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
RO0452294
Intervention Description
Participants received a fixed dose of rituximab, 375 mg/m^2 IV infusion on Day 1 of Cycles 1-6. Post-induction treatment for eligible participants was to be given at a dose of 375 mg/m^2 IV infusion on Day 1 of every other month for up to 6 months, until disease progression or unacceptable toxicity.
Primary Outcome Measure Information:
Title
Percentage of Participants With Complete Response at the End of Induction, Determined by an Independent Review Committee (IRC) on the Basis of Positron Emission Tomography and Computed Tomography (PET-CT) Scans Using Modified Lugano 2014 Criteria
Description
The plan was for the IRC to evaluate responses at the end of induction treatment in participants from the expansion phase 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 indeterminate, 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 to be considered non-responders.
Time Frame
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary Outcome Measure Information:
Title
Number of Participants With a Dose-Limiting Toxicity
Description
A dose-limiting toxicity (DLT) was defined as at least one of the following events occurring during Cycle 1 (or first 2 cycles in the bridging FL cohort) of treatment and assessed by the investigator as not clearly related to the underlying disease: Any Grade 5 adverse event (AE; severity graded per NCI-CTCAE v4.0) unless due to the underlying malignancy or extraneous causes; AE of any grade that leads to a delay of more than (>)14 days in the start of the next treatment cycle; Grade 3 or 4 non-hematologic AEs (with exceptions); Lab results suggestive of potential drug-induced liver injury (according to Hy's law); Grade 3 or 4 neutropenia in the presence of sustained fever of >38 C (lasting >5 days) or a documented infection; Grade 4 neutropenia or thrombocytopenia lasting >7 days; Grade 3 or 4 thrombocytopenia if associated with Grade ≥3 bleeding; Other toxicities considered clinically relevant and related to study treatment as determined by the investigator and medical monitor.
Time Frame
Cycles 1, 2 (1 cycle is 28 days)
Title
Percentage of Participants With Complete Response at the End of Induction, 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 indeterminate, 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
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Title
Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using 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; X = new areas of uptake unlikely to be related to lymphoma). The CR criteria for participants with bone marrow involvement at screening required no evidence of FDG-avid disease in the marrow. 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
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Title
Percentage of Participants With Complete Response at the End of Induction, Determined by the IRC on the Basis of CT Scans Alone Using 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 a complete radiologic response with all of the following: target nodes/nodal masses must regress to less than or equal to 1.5 centimetres 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 had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
Time Frame
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Title
Percentage of Participants With Complete Response at the End of Induction, Determined by the Investigator on the Basis of CT Scans Alone Using 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 centimetres 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 had received at least 2 cycles of induction treatment; those without a post-baseline tumor assessment were to be considered non-responders.
Time Frame
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Title
Percentage of Participants With Objective Response at the End of Induction, Determined by the IRC on the Basis of PET-CT Scans Using Lugano 2014 Criteria
Description
The IRC was to evaluate responses at the 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
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Title
Percentage of Participants With Objective Response at the End of Induction, Determined by the Investigator on the Basis of PET-CT Scans Using Lugano 2014 Criteria
Description
The investigator was to evaluate responses at the 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
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Title
Percentage of Participants With Objective Response at the End of Induction, Determined by an IRC on the Basis of CT Scans Alone Using 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/normal, regressed, but no increase; and spleen must have regressed by >50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time Frame
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Title
Percentage of Participants With Objective Response at the End of Induction, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
Description
The investigator 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/normal, regressed, but no increase; and spleen must have regressed by >50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time Frame
Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Title
Percentage of Participants With Best Response of Complete Response or Partial Response During the Study, Determined by the Investigator on the Basis of CT Scans Alone Using Lugano 2014 Criteria
Description
The investigator was to evaluate responses throughout the study using the Lugano 2014 response criteria for malignant lymphoma for a CT-based best response of 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/normal, regressed, but no increase; and spleen must have regressed by >50% in length. Participants without a post-baseline tumor assessment were to be considered non-responders.
Time Frame
Baseline, Cycle 2, end of induction (up to 6 cycles; 1 cycle is 28 days), every 2 months (FL) until end of maintenance or at 4 months (DLBCL) of consolidation treatment, and then every 6 months during follow-up until disease progression (up to 3.5 years)
Title
Plasma Idasanutlin Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints Grouped by Idasanutlin Dose and Combination Partner (Obinutuzumab or Rituximab)
Description
The concentration of idasanutlin was determined using a validated assay. The duplication of the predose timepoint (0 hours) on Day 5 as an additional 24-hour timepoint on Day 5 was done in order to conduct pharmacokinetics analysis via non-compartmental analysis, and to derive idasanutlin exposure estimates up to the 24-hour post Day 5 dosing.
Time Frame
Predose (0 hours) and 6 hours postdose on Day 1 of Cycles 1, 2, and 4; Predose (0 hours) and 2, 4, 6, and 24 hours postdose on Day 5 of Cycles 1 and 2; Predose (0 hours) and 6 and 24 hours postdose on Cycle 4, Day 5 (1 cycle is 28 days)
Title
Serum Obinutuzumab Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints
Time Frame
Pre-infusion (0 hour) and 0.5 hours after end of obinutuzumab infusion on Day 1 of Cycles 1, 2, 4, and 6
Title
Serum Rituximab Concentrations in DLBCL Participants at Nominal Sampling Timepoints
Time Frame
Pre-infusion (0 hours) at Cycle 1, Day 1 and Cycle 2, Day 1; Post-infusion 0.5 hours at Cycle 1, Day 1 (1 cycle is 28 days)
Title
Safety Summary of the Number of Participants With at Least One Adverse Event by Type and Severity According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)
Description
The adverse event (AE) severity grading scale for the NCI CTCAE v4.0 was used for assessing AE severity. Any AEs that were not specifically listed in the NCI CTCAE, v4.0 were graded per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Time Frame
From first dose until 90 days after the last dose of study drug treatment (up to 31 months)
Title
Baseline Value and Change From Baseline Values of Systolic Blood Pressure at Specified Timepoints
Description
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time Frame
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Title
Baseline Value and Change From Baseline Values of Diastolic Blood Pressure at Specified Timepoints
Description
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time Frame
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Title
Baseline Value and Change From Baseline Values of Pulse Rate at Specified Timepoints
Description
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time Frame
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Title
Baseline Value and Change From Baseline Values of Respiratory Rate at Specified Timepoints
Description
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time Frame
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Title
Baseline Value and Change From Baseline Values of Body Temperature at Specified Timepoints
Description
Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. Maint. = maintenance
Time Frame
Baseline, Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6 (up to 6 cycles; 1 cycle is 28 days), and then every 2 months (FL) or every month (DLBCL) until end of maintenance or consolidation treatment, respectively (up to 29 months)
Title
Number of Participants by Electrocardiogram (ECG) Results Assessment Shift From Baseline to Specified Post-Baseline Timepoints
Description
Single, resting, 12-lead ECG recordings were to be obtained after the participant had been resting in a supine position for at least 10 minutes. Any morphologic waveform changes or other ECG abnormalities were to be documented and clinical significance was determined based on the presence of symptoms, per the investigator's judgment. If the ECG assessment was missing at baseline then it was recorded as "Missing". The ECG results assessments are presented as the shift from baseline to post-baseline assessments at each timepoint. BL = baseline; Cyc1, D1 = Induction Cycle 1 Day 1; Cyc4, D1 = Induction Cycle 4 Day 1; CS = Clinically Significant; EOI = End of Induction Treatment - Completion/Discontinuation; EOM = End of Maintenance Treatment - Completion/Discontinuation; MM1 = Maintenance Month 1; Unsched = Unscheduled Visit
Time Frame
Baseline, Induction Cycle 1 Day 1 and Cycle 4 Day 1, End of Induction (up to 6 cycles; 1 cycle is 28 days); Every 2 months during maintenance treatment from Months 1-23; End of Maintenance (up to 24 months); Unscheduled Visits (as clinically indicated)
Title
Hematology Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
Description
Clinical laboratory tests for hematology parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) at baseline to the highest grade post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a patient with multiple post-baseline abnormalities, the highest (worst) grade for a given lab test is reported. Abs. = absolute count; BL = baseline; WBC = white blood cell count
Time Frame
From Baseline until 35 days after the last dose of study drug (up to 29 months)
Title
Blood Chemistry Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
Description
Clinical laboratory tests for blood chemistry parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) at baseline to the highest grade post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a patient with multiple post-baseline abnormalities, the highest (worst) grade for a given lab test is reported. BL = Baseline; Blood Gluc., Fast. = blood glucose, fasting; SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase; SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase; Triacylglyc. Lipase = triacylglycerol lipase
Time Frame
From Baseline until 35 days after the last dose of study drug (up to 29 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Histologically documented cluster of differentiation (CD) 20-positive B-cell lymphoma classified as relapsed or refractory FL or DLBCL after treatment with at least two prior chemoimmunotherapy regimens that included an anti-CD20 monoclonal antibody (mAb) and for which no other more appropriate treatment option exists At least one bidimensionally measurable lesion Agreement to remain abstinent or use adequate contraception, among women or men of childbearing potential Exclusion Criteria: Known CD20-negative status at relapse or progression Prior allogeneic stem cell transplantation (SCT), or autologous SCT within 100 days prior to Day 1 of Cycle 1 Current use of systemic corticosteroids greater than (>) 20 mg prednisone per day (or equivalent), or prior anti-cancer therapy to include: radioimmunoconjugate within 12 weeks; mAb or antibody-drug conjugate within 4 weeks; or radiotherapy/chemotherapy/hormone therapy/targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1 Requirement for chronic anticoagulation Central nervous system (CNS) disease Active infection Positive for human immunodeficiency virus (HIV) or hepatitis B or C Receipt of a live virus vaccine within 28 days prior to Day 1 of Cycle 1 Poor hematologic, renal, or hepatic function Pregnant or lactating women History of progressive multifocal leukoencephalopathy (PML)
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
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Norton Medical Plaza II
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Swedish Cancer Institute
City
Cary
State/Province
North Carolina
ZIP/Postal Code
27513
Country
United States
Facility Name
Western Pennsylvania Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Guthrie Clinic
City
Sayre
State/Province
Pennsylvania
ZIP/Postal Code
18840
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
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
Zentralklinikum Augsburg
City
Augsburg
ZIP/Postal Code
86156
Country
Germany
Facility Name
Charité Research Organisation GmbH Campus-Virchow-Klinikum
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
SLK-Kliniken Heilbronn GmbH
City
Heilbronn
ZIP/Postal Code
74078
Country
Germany
Facility Name
Universitätsklinikum Köln
City
Köln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Universitätsklinikum Wurzburg
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
National Cancer Center
City
Gyeonggi-do
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
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
North Shore Hospital
City
Auckland
ZIP/Postal Code
0620
Country
New Zealand
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 Idasanutlin in Combination With Obinutuzumab in Relapsed/Refractory (R/R) Follicular Lymphoma (FL) and in Combination With Rituximab in R/R Diffuse Large B-Cell Lymphoma (DLBCL) Participants

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