Safety of PCI-32765 in Chronic Lymphocytic Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01105247
First received: April 13, 2010
Last updated: February 13, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to establish the safety and efficacy of orally administered PCI-32765 in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma.


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Drug: PCI-32765
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Fixed-dose Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: From first dose to within 30 days of last dose of PCI-32765 ] [ Designated as safety issue: Yes ]
    Number of participants who had experienced at least one treatment emergent AEs.


Secondary Outcome Measures:
  • Food Effect Cohort Assessments [ Time Frame: Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design. ] [ Designated as safety issue: No ]
    Geometric mean ratio (Fed/Fasted) for PCI-32765 AUClast. The data were collected at 0, 0.5, 1, 2, 4, 6, 24 h post-dose. The AUClast was calculated from 0 up to 24 hours post-dose.

  • Progression Free Survival Rate at 24 Months [ Time Frame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months). ] [ Designated as safety issue: No ]
    Criteria for progression are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. progression defined as a 50% increase in lymph node size.

  • Percentage of Participants Achieving Response [ Time Frame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months). ] [ Designated as safety issue: No ]
    Response criteria are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. response requires 50% reduction in lymph node size.


Enrollment: 133
Study Start Date: May 2010
Study Completion Date: February 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PCI-32765 Drug: PCI-32765
420 mg daily or 840 mg daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. FOR TREATMENT-NAIVE GROUP ONLY: Men and women ≥ 65 years of age with confirmed diagnosis of CLL/SLL, who require treatment per NCI or International Working Group guidelines 15-18
  2. FOR RELAPSED/REFRACTORY GROUP ONLY: Men and women ≥ 18 years of age with a confirmed diagnosis of relapsed/refractory CLL/SLL following previous therapy(ie, failed ≥ 2 previous treatments for CLL/SLL and at least 1 regimen had to have had a purine analog [eg, fludarabine] for subjects with CLL)
  3. FOR HIGH-RISK RELAPSED/ REFRACTORYGROUP ONLY: Men and women ≥ 18 years of age with a confirmed diagnosis of relapsed/refractory CLL/SLL with suboptimal response to chemoimmunotherapy, defined as progression of disease within 24 months of initiation of a regimen containing at least a nucleoside analogue or bendamustine in combination with a monoclonal antibody or failure to respond to such a regimen. (Note: a minimum of 2 cycles of chemoimmunotherapy required for eligibility)
  4. ECOG performance status of ≤ 2
  5. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty

Exclusion Criteria:

  1. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 2 years or which will not limit survival to < 2 years
  2. Any immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks before first dose of study drug (corticosteroids for disease-related symptoms allowed but require 1-week washout before study drug administration)
  3. Central nervous system (CNS) involvement by lymphoma
  4. Major surgery within 4 weeks before first dose of study drug
  5. Concomitant use of medicines known to cause QT prolongation or torsades de pointes
  6. Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and QTc > 470 msec
  7. Lactating or pregnant
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01105247

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, New York
New York Presbyterian Hosptial Cornell Med Center
New York, New York, United States, 10065
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Oregon
Willamette Valley Cancer Institute and Research Center
Springfield, Oregon, United States, 97477
United States, Tennessee
Sarah Cannon
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Texas Oncology - Tyler
Tyler, Texas, United States, 75702
United States, Vermont
University of Vermont and Fletcher Allen Health Care
Burlington, Vermont, United States, 05405
United States, Washington
Northwest Cancer Specialists, P.C.
Vancouver, Washington, United States, 98686
Yakima Valley Memorial
Yakima, Washington, United States, 98902
Sponsors and Collaborators
Pharmacyclics
Investigators
Study Director: Danelle James, M.D., M.A.S Pharmacyclics
  More Information

Additional Information:
No publications provided by Pharmacyclics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT01105247     History of Changes
Other Study ID Numbers: PCYC-1102-CA, PCI-32765
Study First Received: April 13, 2010
Results First Received: December 16, 2013
Last Updated: February 13, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Pharmacyclics:
PCI-32765
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia, B-Cell
Bruton's Tyrosine Kinase

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014