Text Size

Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients (GL-CLB-001)

This study has been terminated.
(Unsatisfactory enrollment)
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by:
Jewish General Hospital
ClinicalTrials.gov Identifier:
NCT00558961
First received: November 15, 2007
Last updated: April 14, 2010
Last verified: November 2007
History of Changes

November 15, 2007
April 14, 2010
October 2005
April 2009   (final data collection date for primary outcome measure)
Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Measure: Maximum tolerated dose of Gleevec in combination with chlorambucil [ Time Frame: 1 month ]
Complete list of historical versions of study NCT00558961 on ClinicalTrials.gov Archive Site
  • Report adverse events as a measure of safety [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Report response to treatment as a measure of efficacy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Report level of gleevec concentration at different doses as a measure of pharmacokinetics [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Measure: Safety [ Time Frame: 6 months ]
  • Measure: Efficacy [ Time Frame: 6 months ]
  • Measure: Pharmacokinetics [ Time Frame: 1 month ]
Not Provided
Not Provided
 
Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients
A Phase I-II Trial of Gleevec (Imatinib Mesylate) in Combination With Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia (CLL) Patients

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

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.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Lymphocytic Leukemia
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.
Other Names:
  • Gleevec (imatinib mesylate)
  • Chlorambucil
Experimental: I
Gleevec Chlorambucil
Intervention: Drug: Gleevec and Chlorambucil
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
13
April 2009
April 2009   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00558961
CR0506PI, REC:05-054
No
Not Provided
Jewish General Hospital
Novartis Pharmaceuticals
Principal Investigator: Sarit Assouline, MD Jewish General Hospital
Study Director: Lawrence Panasci, MD Jewish General Hospital
Jewish General Hospital
November 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP