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

Condition(s) targeted: Chronic Lymphocytic Leukemia

Intervention: Gleevec and Chlorambucil (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Jewish General Hospital

Official(s) and/or principal investigator(s):
Sarit Assouline, MD, Principal Investigator, Affiliation: Jewish General Hospital
Lawrence Panasci, MD, Study Director, Affiliation: Jewish General Hospital

Overall contact:
Caroline Rousseau, PhD, Phone: 514-340-8222, Ext: 4599, Email: crousseau@ldi.jgh.mcgill.ca

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

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

Study design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Measure: Maximum tolerated dose of Gleevec in combination with chlorambucil

Secondary outcome:

Measure: Safety

Measure: Efficacy

Measure: Pharmacokinetics

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 condiation precluding safe adminstration 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.

Caroline Rousseau, PhD, Phone: 514-340-8222, Ext: 4599, Email: crousseau@ldi.jgh.mcgill.ca

Jewish General Hospital, Montreal, Quebec H4T 1E2, Canada; Recruiting
Caroline Rousseau, PhD, Phone: 514-340-8222, Ext: 4599, Email: crousseau@ldi.jgh.mcgill.ca
Annie Hurtubise, PhD, Phone: 514-340-8222, Ext: 3651, Email: ahurtubise@jgh.mcgill.ca
Sarit Assouline, MD, Principal Investigator

Charles Lemoyne Hospital, Greenfield Park, Quebec J4V 2H1, Canada; Recruiting
Sylvie Parent, Rn, Phone: 450-4666-5000, Ext: 2278, Email: sylvieparent@rrsss16.gouv.qc.ca
Pierre DesJardins, MD, Principal Investigator

Related publications:

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.

Starting date: October 2005
Ending date: April 2009
Last updated: November 15, 2007