Back to resultsSafety of PCI-32765 in Chronic Lymphocytic Leukemia
Primary Purpose
B-cell Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PCI-32765
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Chronic Lymphocytic Leukemia focused on measuring PCI-32765, Lymphoma, B-Cell, Leukemia, Lymphoid, Leukemia, B-Cell, Bruton's Tyrosine Kinase
Eligibility Criteria
Inclusion Criteria:
- 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
- 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)
- 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)
- ECOG performance status of ≤ 2
- Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
Exclusion Criteria:
- 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
- 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)
- Central nervous system (CNS) involvement by lymphoma
- Major surgery within 4 weeks before first dose of study drug
- Concomitant use of medicines known to cause QT prolongation or torsades de pointes
- Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and QTc > 470 msec
- Lactating or pregnant
Sites / Locations
- Stanford University School of Medicine
- New York Presbyterian Hosptial Cornell Med Center
- The Ohio State University
- Willamette Valley Cancer Institute and Research Center
- Sarah Cannon
- MD Anderson Cancer Center
- Texas Oncology - Tyler
- University of Vermont and Fletcher Allen Health Care
- Northwest Cancer Specialists, P.C.
- Yakima Valley Memorial
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PCI-32765
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (AEs)
Number of participants who had experienced at least one treatment emergent AEs.
Secondary Outcome Measures
Food Effect Cohort Assessments
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01105247
Brief Title
Safety of PCI-32765 in Chronic Lymphocytic Leukemia
Official Title
A Phase 1b/2 Fixed-dose Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Chronic Lymphocytic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Keywords
PCI-32765, Lymphoma, B-Cell, Leukemia, Lymphoid, Leukemia, B-Cell, Bruton's Tyrosine Kinase
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
133 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PCI-32765
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
PCI-32765
Intervention Description
420 mg daily or 840 mg daily
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (AEs)
Description
Number of participants who had experienced at least one treatment emergent AEs.
Time Frame
From first dose to within 30 days of last dose of PCI-32765
Secondary Outcome Measure Information:
Title
Food Effect Cohort Assessments
Description
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.
Time Frame
Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design.
Title
Progression Free Survival Rate at 24 Months
Description
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.
Time Frame
The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).
Title
Percentage of Participants Achieving Response
Description
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.
Time Frame
The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
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)
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)
ECOG performance status of ≤ 2
Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
Exclusion Criteria:
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
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)
Central nervous system (CNS) involvement by lymphoma
Major surgery within 4 weeks before first dose of study drug
Concomitant use of medicines known to cause QT prolongation or torsades de pointes
Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and QTc > 470 msec
Lactating or pregnant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Danelle James, M.D., M.A.S
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
New York Presbyterian Hosptial Cornell Med Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center
City
Springfield
State/Province
Oregon
ZIP/Postal Code
97477
Country
United States
Facility Name
Sarah Cannon
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Oncology - Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
University of Vermont and Fletcher Allen Health Care
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05405
Country
United States
Facility Name
Northwest Cancer Specialists, P.C.
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98686
Country
United States
Facility Name
Yakima Valley Memorial
City
Yakima
State/Province
Washington
ZIP/Postal Code
98902
Country
United States
12. IPD Sharing Statement
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Links:
URL
http://www.pharmacyclics.com
Description
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Safety of PCI-32765 in Chronic Lymphocytic Leukemia
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