Safety of PCI-32765 in Chronic Lymphocytic Leukemia

Small Lymphocytic Lymphoma Clinical Trial

Official title:

A Phase 1b/2 Fixed-dose Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01105247
• Other study ID #: PCYC-1102-CA
• Secondary ID: PCI-32765
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 13, 2010
• Last updated: February 13, 2014
• Start date: May 2010
• Est. completion date: February 2013

Study information

• Verified date: February 2014
• Source: Pharmacyclics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: February 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• B-cell Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Small Lymphocytic Lymphoma

Intervention

Drug:
• PCI-32765
420 mg daily or 840 mg daily

Locations

Country	Name	City	State
United States	University of Vermont and Fletcher Allen Health Care	Burlington	Vermont
United States	The Ohio State University	Columbus	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon	Nashville	Tennessee
United States	New York Presbyterian Hosptial Cornell Med Center	New York	New York
United States	Willamette Valley Cancer Institute and Research Center	Springfield	Oregon
United States	Stanford University School of Medicine	Stanford	California
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Northwest Cancer Specialists, P.C.	Vancouver	Washington
United States	Yakima Valley Memorial	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Pharmacyclics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Adverse Events (AEs)	Number of participants who had experienced at least one treatment emergent AEs.	From first dose to within 30 days of last dose of PCI-32765	Yes
Secondary	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.	Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design.	No
Secondary	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.	The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).	No
Secondary	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.	The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).	No

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