Chronic Lymphocytic LeukemiaPhase 1/2GL-CLB-001NCT00558961
Dose Escalation Study of Gleevec and Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia Patients
A Phase 1/2 study testing Gleevec and Chlorambucil in people with Chronic Lymphocytic Leukemia, run by Jewish General Hospital at 2 sites in Canada.
Trial summary
The purpose of this study is to determine maximum tolerated dose of Gleevec in combination with Chlorambucil in previously treated CLL patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Gleevec and Chlorambucil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesCanada
- Study dates
- Oct 2005to Apr 2009
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Charles Lemoyne Hospital
Greenfield Park, Quebec, J4V 2H1
Jewish General Hospital
Montreal, Quebec, H4T 1E2
About this study
Official title: 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.
Read the 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.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Gleevec and Chlorambucil
- Keywords
- CLL, chronic lymphocytic leukemia, leukemia, gleevec, chlorambucil
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gleevec and ChlorambucilDrug
Also called Gleevec (imatinib mesylate), 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.
| Study group | Role | What they receive |
|---|---|---|
| I | Experimental | Gleevec Chlorambucil Receives: Drug: Gleevec and Chlorambucil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil
Measured: 1 month
Secondary outcomes (3)
Report adverse events as a measure of safety
Measured: 6 months
Report response to treatment as a measure of efficacy
Measured: 6 months
Report level of gleevec concentration at different doses as a measure of pharmacokinetics
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2007 (estimated)
- Study startOct 2005
- Primary completionApr 2009
- Study completionApr 2009
Why it stopped: Unsatisfactory enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jewish General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Principal investigator, Sarit Assouline, Jewish General Hospital
- Investigators
- Sarit Assouline, MD, Principal investigator, Jewish General HospitalLawrence Panasci, MD, Study director, Jewish General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00558961
- Sponsor's protocol ID
- CR0506PI
- Other IDs
- REC:05-054
- Acronym
- GL-CLB-001
- Status last verified
- Mar 2023
- First submitted
- 15 Nov 2007
- Last updated
- 27 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1038/sj.leu.2403247.
PubMed 14712290
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Trial of Gleevec (Imatinib Mesylate) in Combination With Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia (CLL) Patients
- ClinicalTrials.gov ID
- NCT00558961
- Acronym / sponsor ID
- GL-CLB-001 / CR0506PI
- Conditions
- Chronic Lymphocytic Leukemia
- Keywords
- CLL, chronic lymphocytic leukemia, leukemia, gleevec, chlorambucil
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unsatisfactory enrollment
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Jewish General HospitalUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Oct 2005
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 16 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| I | Experimental | Drug: Gleevec and ChlorambucilGleevec Chlorambucil |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gleevec and ChlorambucilAlso: Gleevec (imatinib mesylate), ChlorambucilThe 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. | Drug | I |
Primary outcome
Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil
Time frame: 1 month
3 secondary outcomes
Report adverse events as a measure of safety
Time frame: 6 months
Report response to treatment as a measure of efficacy
Time frame: 6 months
Report level of gleevec concentration at different doses as a measure of pharmacokinetics
Time frame: 1 month
Results and safety
The study was stopped early (reason given: Unsatisfactory enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2023.
- Background: PubMed 14712290Aloyz 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarit Assouline, MD principal investigator
Jewish General Hospital
Lawrence Panasci, MD study director
Jewish General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gleevec and Chlorambucil in people with Chronic Lymphocytic Leukemia, run by Jewish General Hospital at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Unsatisfactory enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure number of patients at maximum tolerated dose of Gleevec in combination with chlorambucil (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00558961, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2023.