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

Primary Purpose

Chronic Lymphocytic Leukemia

Status
Terminated
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Gleevec and Chlorambucil
Sponsored by
Jewish General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring CLL, chronic lymphocytic leukemia, leukemia, gleevec, chlorambucil

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Charles Lemoyne Hospital
  • Jewish General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

I

Arm Description

Gleevec Chlorambucil

Outcomes

Primary Outcome Measures

Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil

Secondary Outcome Measures

Report adverse events as a measure of safety
Report response to treatment as a measure of efficacy
Report level of gleevec concentration at different doses as a measure of pharmacokinetics

Full Information

First Posted
November 15, 2007
Last Updated
March 23, 2023
Sponsor
Jewish General Hospital
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00558961
Brief Title
Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Unsatisfactory enrollment
Study Start Date
October 2005 (undefined)
Primary Completion Date
April 2009 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Jewish General Hospital
Collaborators
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
Keywords
CLL, chronic lymphocytic leukemia, leukemia, gleevec, chlorambucil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
I
Arm Type
Experimental
Arm Description
Gleevec Chlorambucil
Intervention Type
Drug
Intervention Name(s)
Gleevec and Chlorambucil
Other Intervention Name(s)
Gleevec (imatinib mesylate), Chlorambucil
Intervention Description
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.
Primary Outcome Measure Information:
Title
Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Report adverse events as a measure of safety
Time Frame
6 months
Title
Report response to treatment as a measure of efficacy
Time Frame
6 months
Title
Report level of gleevec concentration at different doses as a measure of pharmacokinetics
Time Frame
1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sarit Assouline, MD
Organizational Affiliation
Jewish General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lawrence Panasci, MD
Organizational Affiliation
Jewish General Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Charles Lemoyne Hospital
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2H1
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4T 1E2
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
14712290
Citation
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.
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Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients

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