Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients - Full Text View

Sponsor:	Jewish General Hospital
Collaborator:	Novartis Pharmaceuticals
Information provided by:	Jewish General Hospital
ClinicalTrials.gov Identifier:	NCT00558961

Purpose

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

Condition	Intervention	Phase
Chronic Lymphocytic Leukemia	Drug: Gleevec and Chlorambucil	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase I-II Trial of Gleevec (Imatinib Mesylate) in Combination With Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia (CLL) Patients

Resource links provided by NLM:

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Imatinib Imatinib mesylate Chlorambucil

U.S. FDA Resources

Further study details as provided by Jewish General Hospital:

Primary Outcome Measures:

Measure: Maximum tolerated dose of Gleevec in combination with chlorambucil [ Time Frame: 1 month ]

Secondary Outcome Measures:

Measure: Safety [ Time Frame: 6 months ]
Measure: Efficacy [ Time Frame: 6 months ]
Measure: Pharmacokinetics [ Time Frame: 1 month ]

Estimated Enrollment:	34
Study Start Date:	October 2005
Study Completion Date:	April 2009
Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
I: Experimental 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.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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 condiation precluding safe adminstration 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558961

Locations

Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H4T 1E2
Charles Lemoyne Hospital
Greenfield Park, Quebec, Canada, J4V 2H1

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:

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.

Study ID Numbers:	CR0506PI, REC:05-054
Study First Received:	November 15, 2007
Last Updated:	June 12, 2009
ClinicalTrials.gov Identifier:	NCT00558961 History of Changes
Health Authority:	Canada: Health Canada

Keywords provided by Jewish General Hospital:

CLL
chronic lymphocytic leukemia
leukemia
gleevec
chlorambucil

Additional relevant MeSH terms:

Leukemia, Lymphoid
Neoplasms by Histologic Type
Immunoproliferative Disorders
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Chlorambucil
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

Imatinib
Leukemia
Lymphatic Diseases
Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Therapeutic Uses
Antineoplastic Agents, Alkylating
Leukemia, B-Cell
Lymphoproliferative Disorders
Alkylating Agents

ClinicalTrials.gov processed this record on November 22, 2009