- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02888964
Pioglityazone and Imatinib for CML Patients (ACTIM)
A Study to Assess Efficacy and Safety of Pioglitazone as Add-On Therapy to Imatinib Mesylate in CP-CML Patients in Major Molecular Response
This project is a Phase II clinical trial that aims at evaluating efficacy and tolerance of the combination of pioglitazone (Actos®) and imatinib mesylate (STI571, CGP57148, Gleevec®) in patients with Chronic Myelogenous Leukemia (CML) in stable major molecular response (i.e. a BCRABL/ABL ratio assessed by RTQ-PCR equal to or lower than 0.1% according to the European Leukemia Net recommendations) after at least 2 years of therapy with imatinib.
Imatinib mesylate (Gleevec®) is the gold standard for the treatment of CML in chronic phase (O Brian et al. 2003, Druker et al. 2006). Despite a high efficacy of the drug, CML is not eradicated by imatinib alone in almost any of the patients.
Treatment discontinuation in patients treated by imatinib and in complete molecular remission for more than 2 years yield molecular relapses within 6 months in half of the patients,indicating the persistence of CML progenitor cells. STAT5 expression is required for CML stem cell engraftment and expansion in mouse models. STAT5 is the target of the dysregulated activity of BCR-ABL in CML.
Recently, Stephane Prost et al. demonstrated that PPAR-γ is a negative regulator of STAT5A and STAT5B gene expression. Data obtained suggest that PPAR-γ agonists may have potential therapeutic value in reversing myeloproliferative disorders. On the basis of our preclinical studies, we went ahead and administered pioglitazone to one patient who suffered from both diabetes type II and CML with residual disease after continuous treatment with Gleevec. The amount of BCR-ABL transcript detected by QPCR decreased dramatically during the first 3 months of combined (Gleevec + ACTOS) therapy to become undetectable thereafter until 9 months post-treatment, the latest time point assessed. This striking anecdotal result now forms the rationale for filing this formal Phase II clinical trial application.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Annecy, France
- CHR Annecy
-
Bordeaux, France
- Institut Bergonié
-
Le Chesnay, France
- CH Versailles
-
Lille, France
- CHU Lille
-
Marseille, France
- IPC
-
Nice, France
- CHU Archet 1
-
Paris, France
- St Louis
-
Poitiers, France
- CHU Poitiers
-
Toulouse, France
- CHU Purpan
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient aged 18y or more
- Signed informed consent
- Patient with Philadelphia chromosome positive chronic phase CML and M BCR-ABL transcript positivity
- Treatment with imatinib for more than 2 years
- No dose modification of imatinib within the last 3 months
- Complete cytogenetic response on the last cytogenetic analysis within the last 12 months
- Major molecular remission without complete molecular remission
- ECOG grade 0 to 2
- SGOT et SGPT ≤ 2.5 N
- Bilirubin in serum ≤ 1.5 N
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception
Exclusion Criteria:
- Participation in another clinical trial with any investigative drug within 30 days prior to study enrollment
- Prior history of hematopoietic stem cell transplantation (autologous or allogenic)
- Patient requiring anti-diabetic medication
Cardiovascular disease:
- Stage I to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure
- Myocardial infarction within the previous 6 months
- Symptomatic cardiac arrhythmia requiring treatment
- Grade III or IV fluid retention
- Known osteoporosis with therapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ACTOS treatment
Imatinib mesylate at the same daily dose and pioglitazone as add-on therapy at 30 mg/d during 2 months and then 45 mg/d in the absence of serious adverse events
|
Pioglitazone therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The rate of patients achieving a complete molecular response (Sensitivity 10-5 or Bcr Abl/Abl ratio < 0.001 %) 24 weeks after the initiation of pioglitazone, confirmed on by a second determination 2 months later.
Time Frame: 26 weeks
|
26 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Adverse events
Time Frame: 5 years
|
5 years
|
Survival
Time Frame: 5 years
|
5 years
|
Duration of the complete molecular response
Time Frame: 5 years
|
5 years
|
The rate of patients achieving a complete molecular response (Sensitivity 10-5 or Bcr-Abl/Abl ratio < 0.001 %)
Time Frame: 14 months
|
14 months
|
Progression free survival
Time Frame: 5 years
|
5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rousselot Philippe, MD, CH Versailles
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 09/37_ACTIM
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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