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

NCT ID: NCT02624986

Last Updated: 2020-05-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-23
• Study Completion Date: 2019-05-20

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.

Conditions

Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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).

Group Type: EXPERIMENTAL

Obinutuzumab

Intervention Type: DRUG

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.

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

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).

Group Type: EXPERIMENTAL

Idasanutlin

Intervention Type: DRUG

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.

Obinutuzumab

Intervention Type: DRUG

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.

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

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).

Group Type: EXPERIMENTAL

Idasanutlin

Intervention Type: DRUG

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.

Obinutuzumab

Intervention Type: DRUG

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.

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

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).

Group Type: EXPERIMENTAL

Idasanutlin

Intervention Type: DRUG

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.

Rituximab

Intervention Type: DRUG

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.

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

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).

Group Type: EXPERIMENTAL

Idasanutlin

Intervention Type: DRUG

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.

Rituximab

Intervention Type: DRUG

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.

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

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).

Group Type: EXPERIMENTAL

Idasanutlin

Intervention Type: DRUG

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.

Obinutuzumab

Intervention Type: DRUG

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.

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

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).

Group Type: EXPERIMENTAL

Idasanutlin

Intervention Type: DRUG

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.

Obinutuzumab

Intervention Type: DRUG

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.

FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg

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).

Group Type: EXPERIMENTAL

Idasanutlin

Intervention Type: DRUG

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.

Obinutuzumab

Intervention Type: DRUG

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.

Interventions

Idasanutlin

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

Obinutuzumab

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

Rituximab

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.

Intervention Type: DRUG

Other Intervention Names

RO5503781; RO5072759; RO0452294

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

University of Colorado

Aurora, Colorado, United States

Norton Medical Plaza II

Louisville, Kentucky, United States

Swedish Cancer Institute

Cary, North Carolina, United States

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Guthrie Clinic

Sayre, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Prince of Wales Hospital

Randwick, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Linear Clinical Research Limited

Nedlands, Western Australia, Australia

Zentralklinikum Augsburg

Augsburg, , Germany

Charité Research Organisation GmbH Campus-Virchow-Klinikum

Berlin, , Germany

Universitätsklinikum Köln

Cologne, , Germany

SLK-Kliniken Heilbronn GmbH

Heilbronn, , Germany

Universitätsklinikum Wurzburg

Würzburg, , Germany

North Shore Hospital

Auckland, , New Zealand

Christchurch Hospital

Christchurch, , New Zealand

Auckland Clinical Studies Limited

Grafton, , New Zealand

Keimyung University Dongsan Medical Center

Daegu, , South Korea

National Cancer Center

Gyeonggi-do, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Countries

United States; Australia; Germany; New Zealand; South Korea

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-002100-83

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BH29812

Identifier Type: -

Identifier Source: org_study_id