Clinical trial NCT00558961: Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia 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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: CLL
chronic lymphocytic leukemia
leukemia
gleevec
chlorambucil
Lead sponsor: Jewish General Hospital
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2007-11-16
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil
timeFrame: 1 month
Secondary outcomes:
measure: Report adverse events as a measure of safety
timeFrame: 6 months
measure: Report response to treatment as a measure of efficacy
timeFrame: 6 months
measure: Report level of gleevec concentration at different doses as a measure of pharmacokinetics
timeFrame: 1 month
Other outcomes:
Locations:
city: Greenfield Park
country: Canada
facility: Charles Lemoyne Hospital
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: Jewish General Hospital
name: Sarit Assouline, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jewish General Hospital
name: Lawrence Panasci, MD
role: STUDY_DIRECTOR
References:
citation: 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.