Safety of PCI-32765 in Chronic Lymphocytic Leukemia

Phase 1

Completed

• Conditions: Small Lymphocytic Lymphoma; B-cell Chronic Lymphocytic Leukemia
• Interventions: Drug: PCI-32765

• Registration Number: NCT01105247
• Lead Sponsor: Pharmacyclics LLC.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-04-13
• Study First Submitted QC: 2010-04-14
• Study First Posted: 2010-04-16
• Study Start: 2010-05
• Primary Completion: 2012-12
• Study Completion: 2013-02
• Results First Submitted: 2013-12-16
• Status Verified: 2014-02
• Results First Submitted QC: 2014-02-13
• Last Update Submitted: 2014-02-13
• Results First Posted: 2014-03-31
• Last Update Posted: 2014-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 133

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PCI-32765	PCI-32765	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (AEs)	From first dose to within 30 days of last dose of PCI-32765	Number of participants who had experienced at least one treatment emergent AEs.

Secondary Outcome Measures

Name	Time	Method
Food Effect Cohort Assessments	Fed was assessed on either Day 8 or Day 15 and Fasted was assessed on the remaining day as cross-over design.	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	The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 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	The median follow-up time for all treated patients are 21 month, range (0.7 month, 29 months).	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.

Trial Locations

Locations (10)

Sarah Cannon; 🇺🇸 Nashville, Tennessee, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Vermont and Fletcher Allen Health Care; 🇺🇸 Burlington, Vermont, United States

Stanford University School of Medicine; 🇺🇸 Stanford, California, 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

Texas Oncology - Tyler; 🇺🇸 Tyler, Texas, United States

Yakima Valley Memorial; 🇺🇸 Yakima, Washington, United States

Northwest Cancer Specialists, P.C.; 🇺🇸 Vancouver, Washington, United States