Clinical trial NCT02624986: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-12-09
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 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.


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)

Primary outcomes:
measure: 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
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
Secondary outcomes:
measure: Number of Participants With a Dose-Limiting Toxicity
timeFrame: Cycles 1, 2 (1 cycle is 28 days)
measure: 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
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
measure: 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
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
measure: 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
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
measure: 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
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
measure: 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
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
measure: 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
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
measure: 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
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
measure: 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
timeFrame: Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)
measure: 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
timeFrame: 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)
measure: Plasma Idasanutlin Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints Grouped by Idasanutlin Dose and Combination Partner (Obinutuzumab or Rituximab)
timeFrame: 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)
measure: Serum Obinutuzumab Concentrations in DLBCL and FL Participants at Nominal Sampling Timepoints
timeFrame: Pre-infusion (0 hour) and 0.5 hours after end of obinutuzumab infusion on Day 1 of Cycles 1, 2, 4, and 6
measure: Serum Rituximab Concentrations in DLBCL Participants at Nominal Sampling Timepoints
timeFrame: 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)
measure: 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)
timeFrame: From first dose until 90 days after the last dose of study drug treatment (up to 31 months)
measure: Baseline Value and Change From Baseline Values of Systolic Blood Pressure at Specified Timepoints
timeFrame: 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)
measure: Baseline Value and Change From Baseline Values of Diastolic Blood Pressure at Specified Timepoints
timeFrame: 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)
measure: Baseline Value and Change From Baseline Values of Pulse Rate at Specified Timepoints
timeFrame: 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)
measure: Baseline Value and Change From Baseline Values of Respiratory Rate at Specified Timepoints
timeFrame: 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)
measure: Baseline Value and Change From Baseline Values of Body Temperature at Specified Timepoints
timeFrame: 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)
measure: Number of Participants by Electrocardiogram (ECG) Results Assessment Shift From Baseline to Specified Post-Baseline Timepoints
timeFrame: 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)
measure: Hematology Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
timeFrame: From Baseline until 35 days after the last dose of study drug (up to 29 months)
measure: Blood Chemistry Laboratory Test Results Shift Table: Number of Participants by Highest NCI-CTCAE v4.0 Grade at Baseline to Highest Grade Post-Baseline
timeFrame: From Baseline until 35 days after the last dose of study drug (up to 29 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Louisville
country: United States
facility: Norton Medical Plaza II
state: Kentucky
city: Cary
country: United States
facility: Swedish Cancer Institute
state: North Carolina
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Clinic
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Nedlands
country: Australia
facility: Linear Clinical Research Limited
state: Western Australia
city: Augsburg
country: Germany
facility: Zentralklinikum Augsburg
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH Campus-Virchow-Klinikum
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Würzburg
country: Germany
facility: Universitätsklinikum Wurzburg
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Auckland
country: New Zealand
facility: North Shore Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Grafton
country: New Zealand
facility: Auckland Clinical Studies Limited
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: