Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)
A Phase 1b, Multicenter, Open-label, Parallel-group Safety Study of a Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI 32765, in Combination With Chemotherapy in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
2 other identifiers
interventional
33
1 country
6
Brief Summary
The purpose of this study is to establish the safety of orally administered PCI-32765 in combination with fludarabine/cyclophosphamide/rituximab (FCR) and bendamustine/rituximab (BR) in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma(SLL).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2011
Typical duration for phase_1
6 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
Study Start
First participant enrolled
February 1, 2011
CompletedFirst Submitted
Initial submission to the registry
February 2, 2011
CompletedFirst Posted
Study publicly available on registry
February 9, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2013
CompletedResults Posted
Study results publicly available
July 24, 2014
CompletedJuly 24, 2014
July 1, 2014
1.8 years
February 2, 2011
February 28, 2014
July 17, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence of Prolonged Hematologic Toxicity Started in Cycle 1
From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
Secondary Outcomes (6)
Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib
From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0
From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
Overall Incidence of Serious Adverse Events (SAEs)
From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])
From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.
Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline
From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.
- +1 more secondary outcomes
Study Arms (2)
PCI-32765 plus fludarabine/cyclophosphamide/rituximab (FCR)
EXPERIMENTALPCI-32765 plus bendamustine/rituximab (BR)
EXPERIMENTALInterventions
420 mg daily
Eligibility Criteria
You may qualify if:
- Histologically confirmed CLL or SLL and satisfying at least 1 of the following criteria for requiring treatment:
- Progressive splenomegaly and/or lymphadenopathy identified by physical examination or radiographic studies
- Anemia (\<11 g/dL) or thrombocytopenia (\<100,000/μL) due to bone marrow involvement
- Presence of unintentional weight loss \> 10% over the preceding 6 months
- NCI CTCAE Grade 2 or 3 fatigue
- Fevers \> 100.5° or night sweats for \> 2 weeks without evidence of infection
- Progressive lymphocytosis with an increase of \> 50% over a 2 month period or an anticipated doubling time of \< 6 months
- to 3 prior treatment regimens for CLL/SLL
- ECOG performance status of ≤ 1
- ≥ 18 years of age
- Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)
You may not qualify if:
- Any chemotherapy, therapeutic antineoplastic antibodies (not including radio- or toxin immunoconjugates), radiation therapy, or experimental antineoplastic therapy within 4 weeks of first dose of study drug
- Radio- or toxin-conjugated antibody therapy within 10 weeks of first dose of study drug
- Concomitant use of medicines known to cause QT prolongation or torsades de pointes
- Transformed lymphoma or Richter's transformation Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
- Any of the following laboratory abnormalities: oAbsolute neutrophil count (ANC) \< 1000 cells/mm3 (1.0 x 109/L) oPlatelet count \< 50,000/mm3 (50 x 109/L) oSerum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) oCreatinine \> 2.0 x ULN or creatinine clearance \< 40 mL/min
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Dana Farber Cancer Center
Boston, Massachusetts, 02115, United States
CLL Research and Treatment Program
New Hyde Park, New York, 11042, United States
Weill Medical College of Cornell University
New York, New York, 10065, United States
University of Rochester
Rochester, New York, 14642, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
MD Anderson
Houston, Texas, 77030, United States
Related Publications (1)
Brown JR, Barrientos JC, Barr PM, Flinn IW, Burger JA, Tran A, Clow F, James DF, Graef T, Friedberg JW, Rai K, O'Brien S. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Blood. 2015 May 7;125(19):2915-22. doi: 10.1182/blood-2014-09-585869. Epub 2015 Mar 9.
PMID: 25755291DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Thorsten Graef, MD
- Organization
- Pharmacyclics
Study Officials
- STUDY DIRECTOR
Thorsten Graef, MD
Pharmacyclics LLC.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
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
February 2, 2011
First Posted
February 9, 2011
Study Start
February 1, 2011
Primary Completion
November 1, 2012
Study Completion
May 1, 2013
Last Updated
July 24, 2014
Results First Posted
July 24, 2014
Record last verified: 2014-07