Chronic Lymphocytic Leukemia
Conditions
Keywords
CLL, chronic lymphocytic leukemia, leukemia, gleevec, chlorambucil
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.
Interventions
DRUGGleevec 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.
Sponsors
Novartis Pharmaceuticals
Jewish General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil | 1 month |
Secondary
| Measure | Time frame |
|---|---|
| Report adverse events as a measure of safety | 6 months |
| Report response to treatment as a measure of efficacy | 6 months |
| Report level of gleevec concentration at different doses as a measure of pharmacokinetics | 1 month |
Countries
Canada
Outcome results
None listed