Pioglityazone and Imatinib for CML Patients (ACTIM)
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|ClinicalTrials.gov Identifier: NCT02888964|
Recruitment Status : Completed
First Posted : September 5, 2016
Last Update Posted : September 8, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia, Myeloid, Chronic-Phase||Drug: Add-on therapy||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study to Assess Efficacy and Safety of Pioglitazone as Add-On Therapy to Imatinib Mesylate in CP-CML Patients in Major Molecular Response|
|Study Start Date :||December 2009|
|Actual Primary Completion Date :||February 2012|
|Actual Study Completion Date :||February 2016|
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
Drug: Add-on therapy
- 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 ]
- Adverse events [ Time Frame: 5 years ]
- Duration of the complete molecular response [ Time Frame: 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 ]
- Survival [ Time Frame: 5 years ]
- Progression free survival [ Time Frame: 5 years ]
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): NCT02888964
|Le Chesnay, France|
|CHU archet 1|
|Principal Investigator:||Rousselot Philippe, MD||CH Versailles|