Ibrutinib in Combination With Lenalidomide and Rituximab in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

NCT ID: NCT02077166

Last Updated: 2022-02-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-13

Study Completion Date

2020-12-17

Brief Summary

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This Phase 1b/2 study is designed to assess the safety and efficacy of ibrutinib in combination with lenalidomide and rituximab in subjects with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not eligible for transplant.

Detailed Description

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Phase 1b: In the dose escalation portion of the study, various cohorts with escalating doses of lenalidomide may be explored, using the 3+3+3 principle for dose determination.

Phase 2: This will be conducted as an international, multicenter, open-label study. Eligible subjects will receive ibrutinib, lenalidomide and rituximab.

Conditions

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Relapsed Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1)

Ibrutinib 560 mg administered orally (PO) once daily (QD) beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 15 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered intravenously (IV) on Day 1 of each 28-day cycle for 6 cycles.

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Phase 1b: Enrolled at Lenalidomide Dose 10 mg (Dose Level -1)

De-escalation cohort: Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 10 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1+)

Re-escalation cohort: Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 15 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Phase 1b: Enrolled at Lenalidomide Dose 20 mg (Dose Level 2)

Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 20 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Phase 1b: Enrolled at Lenalidomide Dose 25 mg (Dose Level 3)

Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 25 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Phase 2: Enrolled at Lenalidomide Dose 20 mg

Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 20 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Phase 2: Enrolled at Lenalidomide Dose 25 mg

Ibrutinib 560 mg administered PO QD beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 25 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered IV on Day 1 of each 28-day cycle for 6 cycles.

Group Type EXPERIMENTAL

Ibrutinib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Interventions

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Ibrutinib

Intervention Type DRUG

Lenalidomide

Intervention Type DRUG

Rituximab

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Pathologically confirmed relapsed/ refractory DLBCL
* Must have previously received first line treatment regimen
* Must be ineligible for high dose therapy/ stem cell transplantation
* Measurable disease sites on computed tomography (CT) scan (\>1.5 cm in longest dimension)
* prothrombin time/international normalized ratio (PT/INR) \< 1.5 x upper limit of normal (ULN) and partial thromboplastin time (PTT; activated partial thromboplastin time \[aPTT\]) \<1.5 x ULN
* Men and women ≥18 years of age
* Eastern Cooperative Oncology Group (ECOG) \< 2
* Adequate hepatic and renal function
* Adequate hematologic function

Exclusion Criteria

* Medically apparent central nervous system lymphoma or leptomeningeal disease
* History of allogeneic stem-cell (or other organ) transplantation
* Any chemotherapy, external beam radiation therapy, or anticancer antibodies within 2 weeks
* Radio- or toxin-immunoconjugates within 10 weeks
* Concurrent enrollment in another therapeutic investigational study or have previously taken ibrutinib and/or lenalidomide.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role collaborator

Celgene Corporation

INDUSTRY

Sponsor Role collaborator

Pharmacyclics LLC.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jutta K. Neuenburg, MD, PhD

Role: STUDY_DIRECTOR

Pharmacyclics LLC.

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Cedar Sinai Medical Center

Los Angeles, California, United States

Site Status

UCLA Medical Center

Los Angeles, California, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Tulane Medical Center

New Orleans, Louisiana, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Summit Medical Group

Morristown, New Jersey, United States

Site Status

Weill Cornell Medical Center

New York, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

University of Cincinnati Health Barrett Center

Cincinnati, Ohio, United States

Site Status

Mid-Ohio Oncology/ Hematology

Columbus, Ohio, United States

Site Status

University of TN Medical Center

Knoxville, Tennessee, United States

Site Status

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Baylor Charles Sammons Cancer Center

Dallas, Texas, United States

Site Status

The University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Medical Oncology Associates, PS

Spokane, Washington, United States

Site Status

Northwest Medical Specialities, PLLC

Tacoma, Washington, United States

Site Status

Ziekenhuis Netwerk Antwerpen - Campus Stuivenberg

Antwerp, , Belgium

Site Status

CHU Brugmann

Brussels, , Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Universiaetsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Site Status

Klinikum der Universitaet Muenchen - Campus Grosshadern

Munich, Bavaria, Germany

Site Status

Klinikum rechts der Isar - Technische Universitaet Muenchen, III. Medizinische Klinik und Polyklinik

Munich, Bavaria, Germany

Site Status

Universitaetsklinikum Wuerzburg, Medizinische Klinik und Poliklinik II

Würzburg, Bavaria, Germany

Site Status

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

Northwick Park Hospital

Harrow, , United Kingdom

Site Status

The Leeds Teaching Hospitals

Leeds, , United Kingdom

Site Status

Kings College Hospital

London, , United Kingdom

Site Status

University College London Hospitals

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Site Status

Countries

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United States Belgium Germany United Kingdom

References

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Ramchandren R, Johnson P, Ghosh N, Ruan J, Ardeshna KM, Johnson R, Verhoef G, Cunningham D, de Vos S, Kassam S, Fayad L, Radford J, Bailly S, Offner F, Morgan D, Munoz J, Ping J, Szafer-Glusman E, Eckert K, Neuenburg JK, Goy A. The iR2 regimen (ibrutinib plus lenalidomide and rituximab) for relapsed/refractory DLBCL: A multicentre, non-randomised, open-label phase 2 study. EClinicalMedicine. 2022 Dec 26;56:101779. doi: 10.1016/j.eclinm.2022.101779. eCollection 2023 Feb.

Reference Type DERIVED
PMID: 36618900 (View on PubMed)

Goy A, Ramchandren R, Ghosh N, Munoz J, Morgan DS, Dang NH, Knapp M, Delioukina M, Kingsley E, Ping J, Beaupre DM, Neuenburg JK, Ruan J. Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed/refractory non-germinal center B-cell-like DLBCL. Blood. 2019 Sep 26;134(13):1024-1036. doi: 10.1182/blood.2018891598. Epub 2019 Jul 22.

Reference Type DERIVED
PMID: 31331917 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-004341-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PCYC-1123-CA

Identifier Type: -

Identifier Source: org_study_id

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