Safety and Efficacy Study of a BTK Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma
A Multicenter, Open-label, Phase 2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Refractory or de Novo Diffuse Large B-cell Lymphoma (DLBCL)
2 other identifiers
interventional
78
1 country
15
Brief Summary
The purpose of this study is to evaluate the efficacy of ibrutinib (PCI-32765) in relapsed/refractory de novo activated B-cell (ABC) and germinal-cell B-Cell (GCB) Diffuse Large B-cell Lymphoma (DLBCL).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2011
Typical duration for phase_2
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 2, 2011
CompletedFirst Posted
Study publicly available on registry
March 30, 2011
CompletedStudy Start
First participant enrolled
May 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2014
CompletedResults Posted
Study results publicly available
February 16, 2017
CompletedMarch 31, 2017
March 1, 2017
3.4 years
February 2, 2011
June 30, 2016
March 2, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Patients With an Overall Response to Study Drug
The primary endpoint of the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR), according to the revised International Working Group Criteria for non-Hodgkin's lymphoma (Cheson et al, 2007), as assessed by the investigator.
The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 months)
Secondary Outcomes (2)
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Adverse events determined to be related to study drug are collected from first dose until study exit (approximately 3 years).
Ibrutinib and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765
Performed during the first month of receiving study drug.
Study Arms (2)
PCI-32765: 560 mg
EXPERIMENTALTreatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.
PCI-32765: 840 mg
EXPERIMENTALTreatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.
Interventions
ibrutinib is an inhibitor of BTK
Eligibility Criteria
You may qualify if:
- Men and women ≥ 18 years of age.
- ECOG performance status ≤ 2.
- Pathologically confirmed de novo DLBCL
- Subjects must have available tissue for central pathology review to be eligible. Treatment Group 2: Subjects will be eligible if they have the non-GCB phenotype, as confirmed by Central IHC testing by the Hans method.
- Relapsed or refractory disease, defined as either: 1) recurrence of disease after a CR, or 2) PR, SD, or progressive disease (PD) at completion of the treatment regimen preceding entry to the study (residual disease): Subjects must have previously received an appropriate first-line treatment regimen. Subjects who have not received HDT/ASCT must be ineligible for HDT/ASCT
- Treatment Group 1: Subjects must have ≥ 1 measurable (\> 2 cm in longest dimension) disease sites on CT scan. Treatment Group 2: Subjects must have ≥ 1 measurable (\> 1.5 cm in longest dimension) disease sites on CT scan.
You may not qualify if:
- Transformed DLBCL or DLBCL with coexistent histologies (eg, FL or MALT).
- Primary mediastinal (thymic) large B-cell lymphoma.
- Major surgery within 2 weeks of first dose of study drug.
- Any of the following laboratory abnormalities:
- ANC \< 0.75 x 10\^9/L. Treatment Group 2: Eligible subjects must be independent of growth factor support for 7 days prior to the screening lab tests.
- Platelet count \< 50 x 10\^9/L independent of transfusion support. Treatment Group 2 only: Eligible subjects must be independent of transfusion support for 7 days prior to the screening lab tests.
- AST or ALT ≥ 3.0 x upper limit of normal (ULN)
- Creatinine \> 2.0 x ULN
- Treatment Group 2 only: Hemoglobin \< 8.0 g/dL
- Treatment Group 2 only: Total Bilirubin \> 1.5 x ULN
- Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon)
- Treatment Group 2: Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
- Treatment Group 2: Known bleeding diathesis, eg, von Willebrand's disease, hemophilia.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
UCLA Medical Center
Los Angeles, California, 90095, United States
Stanford University School of Medicine
Stanford, California, 94305, United States
National Cancer Institute
Bethesda, Maryland, 20892-1203, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Long Island Jewish Medical Center
New Hyde Park, New York, 11042, United States
New York University
New York, New York, 10016, United States
Weill Medical College of Cornell University
New York, New York, 10021, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester School of Medicine and Dentistry
Rochester, New York, 14642, United States
The Ohio Sate university
Columbus, Ohio, 43210, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Univerity of Washington
Seattle, Washington, 98109, United States
University of Wisconsin
Madison, Wisconsin, 53705, United States
Related Publications (1)
Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. doi: 10.1038/nm.3884. Epub 2015 Jul 20.
PMID: 26193343DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
PCI-32765:840 mg:8 subjects were enrolled and followed through their 1st response assessment. Due to a lack of positive responses observed, enrollment was terminated for futility. Response rate should not be generalized due to small sample size.
Results Point of Contact
- Title
- Dr. Darrin Beaupre
- Organization
- Pharmacyclics, Inc.
Study Officials
- STUDY DIRECTOR
Darrin Beaupre, MD
Pharmacyclics LLC.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 2, 2011
First Posted
March 30, 2011
Study Start
May 1, 2011
Primary Completion
October 1, 2014
Study Completion
October 1, 2014
Last Updated
March 31, 2017
Results First Posted
February 16, 2017
Record last verified: 2017-03
Data Sharing
- IPD Sharing
- Will not share