Ignite Creation Date:
2024-05-06 @ 9:01 AM
Last Modification Date:
2024-10-26 @ 12:09 PM
Study NCT ID:
NCT02888964
Status:
COMPLETED
Last Update Posted:
2016-09-08
First Post:
2016-08-19
Brief Title:
Pioglityazone and Imatinib for CML Patients
Sponsor:
Versailles Hospital
Organization:
Versailles Hospital
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2016-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ACTIM
Brief Summary:
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 ie a BCRABLABL ratio assessed by RTQ-PCR equal to or lower than 01 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 patientsindicating 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
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 patientsindicating 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None