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

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ClinicalTrials.gov Identifier: NCT00558961
Recruitment Status : Terminated (Unsatisfactory enrollment)
First Posted : November 16, 2007
Last Update Posted : April 15, 2010
Sponsor:
Collaborator:
Information provided by:

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

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Gleevec and Chlorambucil Phase 1 Phase 2

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I-II Trial of Gleevec (Imatinib Mesylate) in Combination With Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia (CLL) Patients
Study Start Date : October 2005
Primary Completion Date : April 2009
Study Completion Date : April 2009


Arms and Interventions

Arm Intervention/treatment
Experimental: I
Gleevec Chlorambucil
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


Outcome Measures

Primary Outcome Measures :
  1. Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil [ Time Frame: 1 month ]

Secondary Outcome Measures :
  1. Report adverse events as a measure of safety [ Time Frame: 6 months ]
  2. Report response to treatment as a measure of efficacy [ Time Frame: 6 months ]
  3. Report level of gleevec concentration at different doses as a measure of pharmacokinetics [ Time Frame: 1 month ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00558961


Locations
Canada, Quebec
Charles Lemoyne Hospital
Greenfield Park, Quebec, Canada, J4V 2H1
Jewish General Hospital
Montreal, Quebec, Canada, H4T 1E2
Sponsors and Collaborators
Jewish General Hospital
Novartis Pharmaceuticals
Investigators
Principal Investigator: Sarit Assouline, MD Jewish General Hospital
Study Director: Lawrence Panasci, MD Jewish General Hospital
More Information

Publications:
ClinicalTrials.gov Identifier: NCT00558961     History of Changes
Other Study ID Numbers: CR0506PI
REC:05-054
First Posted: November 16, 2007    Key Record Dates
Last Update Posted: April 15, 2010
Last Verified: November 2007

Keywords provided by Jewish General Hospital:
CLL
chronic lymphocytic leukemia
leukemia
gleevec
chlorambucil

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Imatinib Mesylate
Chlorambucil
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents