Clinical trial NCT02077166: Ibrutinib in Combination With Lenalidomide and Rituximab in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Official title: A Multicenter Open-Label Phase 1b/2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Lenalidomide and Rituximab in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Relapsed Diffuse Large B-Cell Lymphoma
Refractory Diffuse Large B-Cell Lymphoma
Keywords: DLBCL
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
name: Celgene Corporation
First posted: 2014-03-04
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1b: Recommended Phase 2 Dose of Lenalidomide in Combination With Fixed Doses of Ibrutinib and Rituximab in Participants With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
timeFrame: Estimated median time on study in Phase 1b was 59.6 months.
measure: Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
timeFrame: From first dose of study drug up to 30 days after last dose of study drug. Phase 1b median duration of ibrutinib exposure was 4.4 months; median duration of lenalidomide exposure was 4.4 months; median total number of doses of rituximab received was 4.0.
measure: Phase 2: Overall Response Rate (ORR)
timeFrame: Estimated median time on study in Phase 2 was 35.0 months.
Secondary outcomes:
measure: Phase 1b: ORR
timeFrame: Estimated median time on study in Phase 1b was 59.6 months.
measure: Phase 1b: Complete Response (CR) Rate
timeFrame: Estimated median time on Phase 1b study was 59.6 months.
measure: Phase 2: CR Rate
timeFrame: Estimated median time on study in Phase 2 was 35.0 months.
measure: Phase 2: Duration of Response (DOR)
timeFrame: Estimated median time on study in Phase 2 was 35.0 months.
measure: Phase 2: Progression Free Survival (PFS)
timeFrame: Estimated median time on study in Phase 2 was 35.0 months.
measure: Phase 2: Overall Survival (OS)
timeFrame: Estimated median time on study in Phase 2 was 35.0 months.
measure: Phase 2: Number of Participants With TEAEs, Serious TEAEs, and Discontinuations Due to TEAEs
timeFrame: From first dose of study drug up to 30 days after last dose of study drug. Phase 2 median duration of ibrutinib exposure was 4.9 months; median duration of lenalidomide exposure was 4.7 months; median total number of doses of rituximab received was 5.0.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedar Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Center of Nevada
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Summit Medical Group
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Health Barrett Center
state: Ohio
city: Columbus
country: United States
facility: Mid-Ohio Oncology/ Hematology
state: Ohio
city: Knoxville
country: United States
facility: University of TN Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Charles Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas, MD Anderson Cancer Center
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates, PS
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialities, PLLC
state: Washington
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen - Campus Stuivenberg
city: Brussels
country: Belgium
facility: CHU Brugmann
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Ulm
country: Germany
facility: Universiaetsklinikum Ulm
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen - Campus Grosshadern
state: Bayern
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar - Technische Universitaet Muenchen, III. Medizinische Klinik und Polyklinik
state: Bayern
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg, Medizinische Klinik und Poliklinik II
state: Bayern
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: University College London Hospitals
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Pharmacyclics LLC.
name: Jutta K. Neuenburg, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.