Leukemia, Myeloid, Chronic-Phase Clinical Trial
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
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.
n/a
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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