Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients

Phase 1

Terminated

• Conditions: Chronic Lymphocytic Leukemia
• Interventions: Drug: Gleevec and Chlorambucil

• Registration Number: NCT00558961
• Lead Sponsor: Jewish General Hospital

Brief Summary

The purpose of this study is to determine maximum tolerated dose of Gleevec in combination with Chlorambucil in previously treated CLL patients.

Detailed Description

A recent study by Aloyz et al demonstrated a synergistic effect of imatinib on chlorambucil-mediated cytotoxicity in CLL cells in vitro. Imatinib inhibits c-abl and sensitizes cells to chlorambucil. The Phase I component of the study will determine the maximum tolerated dose and recommended Phase II dose of Gleevec when used in combination with chlorambucil. Once the maximum tolerated dose has been determined, a total of 16 patients will be enrolled in the Phase II component of the study. This study will determine the dose limiting toxicities, pharmacokinetics and pharmacodynamics of Gleevec in combination with chlorambucil.

Study Timeline

• Study Start: 2005-10
• Study First Submitted: 2007-11-15
• Study First Submitted QC: 2007-11-15
• Study First Posted: 2007-11-16
• Primary Completion: 2009-04
• Study Completion: 2009-04
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-23
• Last Update Posted: 2023-03-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

• B-cell chronic lymphocytic leukemia (a) Rai stage 0-II with indication for treatment by NCI Working Group Criteria: or (b) Rai stage III or IV.
• Received a minimum of one prior chemotherapy regimen. Prior treatment with corticosteroids, immunotherapies, monoclonal antibodies or radiation therapy is permitted.
• White blood cell count > 25 x 10^9/L
• ECOG 0, 1,or 2.
• Adequate renal and hepatic function
• Platelets > 75 x 10^9/L, transfusion independent.
• Neutrophils > 1.0 x 10^9/L, transfusion independent

Exclusion Criteria

• Documented prolymphocytic leukemia (PLL; prolymphocytes, 55% in blood)
• Active cardiovascular disease as defined by NYHA class III-IV categorization.
• Intercurrent illness or medical condition precluding safe administration of ribavirin.
• Concurrent use of chronic steroids, except as replacement therapy for adrenal insufficiency
• Known infection with HIV, Hepatitis B or C.
• Concurrent malignancy (other than resected basal or squamous cell skin cancers or in-situ carcinoma).
• Received any previous therapy for CLL within 28 days prior to study entry.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
I	Gleevec and Chlorambucil	Gleevec Chlorambucil

Primary Outcome Measures

Name	Time	Method
Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil	1 month

Secondary Outcome Measures

Name	Time	Method
Report level of gleevec concentration at different doses as a measure of pharmacokinetics	1 month
Report response to treatment as a measure of efficacy	6 months
Report adverse events as a measure of safety	6 months

Trial Locations

Locations (2)

Charles Lemoyne Hospital; 🇨🇦 Greenfield Park, Quebec, Canada

Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada