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

NCT02624986 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: BH298122015-002100-83
• Study Type: interventional
• Target: 25
• Locations: 5 countries
• Sites: 24

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)

Secondary Outcomes (22)

• Number of Participants With a Dose-Limiting Toxicity

  Cycles 1, 2 (1 cycle is 28 days)

• 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

  Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)

• 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

  Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)

• 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

  Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)

• 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

  Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 28 weeks; 1 cycle is 28 days)

Study Arms (8)

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

EXPERIMENTAL

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).

Drug: Obinutuzumab

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

EXPERIMENTAL

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).

Drug: Idasanutlin; Drug: Obinutuzumab

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

EXPERIMENTAL

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).

Drug: Idasanutlin; Drug: Obinutuzumab

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

EXPERIMENTAL

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).

Drug: Idasanutlin; Drug: Rituximab

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

EXPERIMENTAL

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).

Drug: Idasanutlin; Drug: Rituximab

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

EXPERIMENTAL

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).

Drug: Idasanutlin; Drug: Obinutuzumab

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

EXPERIMENTAL

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).

Drug: Idasanutlin; Drug: Obinutuzumab

FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg

EXPERIMENTAL

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).

Drug: Idasanutlin; Drug: Obinutuzumab

Interventions

Idasanutlin 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.

Also known as: RO5503781

DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2; DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2; DLBCL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg; DLBCL Non-Bridging: Idasanutlin 200 mg + Obinutuzumab 1000 mg; FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg; FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg; FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg

Obinutuzumab 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.

Also known as: RO5072759

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; FL Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg; FL Non-Bridging: Idasanutlin 100 mg + Obinutuzumab 1000 mg; FL Non-Bridging: Idasanutlin 150 mg + Obinutuzumab 1000 mg

Rituximab 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.

Also known as: RO0452294

DLBCL Bridging: Idasanutlin 150 mg + Rituximab 375 mg/m^2; DLBCL Bridging: Idasanutlin 200 mg + Rituximab 375 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (24)

Mayo Clinic Arizona

Phoenix, Arizona, 85259, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Norton Medical Plaza II

Louisville, Kentucky, 40207, United States

Location

Swedish Cancer Institute

Cary, North Carolina, 27513, United States

Location

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Guthrie Clinic

Sayre, Pennsylvania, 18840, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Linear Clinical Research Limited

Nedlands, Western Australia, 6009, Australia

Location

Zentralklinikum Augsburg

Augsburg, 86156, Germany

Location

Charité Research Organisation GmbH Campus-Virchow-Klinikum

Berlin, 13353, Germany

Location

Universitätsklinikum Köln

Cologne, 50937, Germany

Location

SLK-Kliniken Heilbronn GmbH

Heilbronn, 74078, Germany

Location

Universitätsklinikum Wurzburg

Würzburg, 97080, Germany

Location

North Shore Hospital

Auckland, 0620, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Auckland Clinical Studies Limited

Grafton, 1010, New Zealand

Location

Keimyung University Dongsan Medical Center

Daegu, 41931, South Korea

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

RG7388; obinutuzumab; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Due to the overall modest benefit achieved with the maximum tolerated dose during the dose escalation phase, the Sponsor decided not to open the expansion phase and terminated the study. Consequently, some planned analyses could not be performed.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 9, 2015
• Study Start: December 23, 2015
• Primary Completion: May 20, 2019
• Study Completion: May 20, 2019
• Last Updated: May 18, 2020
• Results First Posted: April 29, 2020

Record last verified: 2020-04

Locations

US (8); DE (5); AU (3); KR (5); NZ (3)