Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients (GL-CLB-001)

March 23, 2023 updated by: Sarit Assouline, Jewish General Hospital

A Phase I-II Trial of Gleevec (Imatinib Mesylate) in Combination With Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia (CLL) Patients

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • Charles Lemoyne Hospital
      • Montreal, Quebec, Canada, H4T 1E2
        • Jewish General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: I
Gleevec Chlorambucil
Drug: Gleevec and Chlorambucil
The first cohort will receive Gleevec at 300 mg daily on days 1-10 and chlorambucil 8mg/m2/d from day 3-7. This will be repeated every 28 days. Cohort 2 will receive 400 mg Gleevec and Cohort 3 will receive 600 mg Gleevec. Each dose level may be expanded up to 6 patients if 1 of 3 patients experiences any dose limiting toxicities.
Other Names:
  • Gleevec (imatinib mesylate)
  • Chlorambucil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil
Time Frame: 1 month
1 month

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jewish General Hospital

Collaborators

Novartis Pharmaceuticals

Investigators

  • Study Director: Lawrence Panasci, MD, Jewish General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2005

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

November 15, 2007

First Submitted That Met QC Criteria

November 15, 2007

First Posted (Estimate)

November 16, 2007

Study Record Updates

Last Update Posted (Actual)

March 27, 2023

Last Update Submitted That Met QC Criteria

March 23, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR0506PI
  • REC:05-054

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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