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

Chronic Lymphocytic Leukemia Clinical Trial

— GL-CLB-001  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00558961
• Other study ID #: CR0506PI
• Secondary ID: REC:05-054
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: October 2005
• Est. completion date: April 2009

Study information

• Verified date: March 2023
• Source: Jewish General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Canada	Charles Lemoyne Hospital	Greenfield Park	Quebec
Canada	Jewish General Hospital	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Jewish General Hospital	Novartis Pharmaceuticals

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil		1 month
Secondary	Report adverse events as a measure of safety		6 months
Secondary	Report response to treatment as a measure of efficacy		6 months
Secondary	Report level of gleevec concentration at different doses as a measure of pharmacokinetics		1 month