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

Roche

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Non-Hodgkin's Lymphoma

Treatments: Drug: Idasanutlin; Drug: Rituximab; Drug: Obinutuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02624986

2015-002100-83 (EudraCT Number)

BH29812

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 8 patient groups

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

Experimental group

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).

Treatment:

Drug: Obinutuzumab

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

Experimental group

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).

Treatment:

Drug: Obinutuzumab

Drug: Idasanutlin

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

Experimental group

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).

Treatment:

Drug: Obinutuzumab

Drug: Idasanutlin

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

Experimental group

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).

Treatment:

Drug: Rituximab

Drug: Idasanutlin

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

Experimental group

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).

Treatment:

Drug: Rituximab

Drug: Idasanutlin

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

Experimental group

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).

Treatment:

Drug: Obinutuzumab

Drug: Idasanutlin

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

Experimental group

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).

Treatment:

Drug: Obinutuzumab

Drug: Idasanutlin

FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg

Experimental group

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).

Treatment:

Drug: Obinutuzumab

Drug: Idasanutlin