Clinical trial NCT01105247: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: B-cell Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: PCI-32765
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia, B-Cell
Bruton's Tyrosine Kinase
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2010-04-16
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: From first dose to within 30 days of last dose of PCI-32765
Secondary outcomes:
measure: Food Effect Cohort Assessments
timeFrame: Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design.
measure: Progression Free Survival Rate at 24 Months
timeFrame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).
measure: Percentage of Participants Achieving Response
timeFrame: The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: New York
country: United States
facility: New York Presbyterian Hosptial Cornell Med Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Springfield
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Burlington
country: United States
facility: University of Vermont and Fletcher Allen Health Care
state: Vermont
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial
state: Washington
Study officials:
affiliation: Pharmacyclics LLC.
name: Danelle James, M.D., M.A.S
role: STUDY_DIRECTOR
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