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

NCT ID: NCT00558961

Last Updated: 2023-03-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2009-04-30

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

I

Gleevec Chlorambucil

Group Type: EXPERIMENTAL

Gleevec and Chlorambucil

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Gleevec (imatinib mesylate); Chlorambucil

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Jewish General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sarit Assouline

Associate Professor, Department of Oncology, McGill University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sarit Assouline, MD

Role: PRINCIPAL_INVESTIGATOR

Jewish General Hospital

Lawrence Panasci, MD

Role: STUDY_DIRECTOR

Jewish General Hospital

Locations

Charles Lemoyne Hospital

Greenfield Park, Quebec, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Countries

Canada

References

Aloyz R, Grzywacz K, Xu ZY, Loignon M, Alaoui-Jamali MA, Panasci L. Imatinib sensitizes CLL lymphocytes to chlorambucil. Leukemia. 2004 Mar;18(3):409-14. doi: 10.1038/sj.leu.2403247.

Reference Type: BACKGROUND

PMID: 14712290 (View on PubMed)

Other Identifiers

REC:05-054

Identifier Type: -

Identifier Source: secondary_id

CR0506PI

Identifier Type: -

Identifier Source: org_study_id