Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients
Information source: Jewish General Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Lymphocytic Leukemia
Intervention: Gleevec and Chlorambucil (Drug)
Phase: Phase 1/Phase 2
Status: Terminated
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
Summary
The purpose of this study is to determine maximum tolerated dose of Gleevec in combination
with Chlorambucil in previously treated CLL patients.
Clinical Details
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: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil
Secondary outcome: Report adverse events as a measure of safetyReport response to treatment as a measure of efficacy Report level of gleevec concentration at different doses as a measure of 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.
Eligibility
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 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.
Locations and Contacts
Charles Lemoyne Hospital, Greenfield Park, Quebec J4V 2H1, Canada
Jewish General Hospital, Montreal, Quebec H4T 1E2, Canada
Additional Information
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
Last updated: April 14, 2010
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