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Pioglityazone and Imatinib for CML Patients (ACTIM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02888964
Recruitment Status : Completed
First Posted : September 5, 2016
Last Update Posted : September 8, 2016
Sponsor:
Information provided by (Responsible Party):
Philippe ROUSSELOT, Versailles Hospital

Study Description
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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 (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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
 Drug: Add-on therapy
Pioglitazone therapy


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 5 years ]
  2. Duration of the complete molecular response [ Time Frame: 5 years ]
  3. The rate of patients achieving a complete molecular response (Sensitivity 10-5 or Bcr-Abl/Abl ratio < 0.001 %) [ Time Frame: 14 months ]
  4. Survival [ Time Frame: 5 years ]
  5. Progression free survival [ Time Frame: 5 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient aged 18y or more
  2. Signed informed consent
  3. Patient with Philadelphia chromosome positive chronic phase CML and M BCR-ABL transcript positivity
  4. Treatment with imatinib for more than 2 years
  5. No dose modification of imatinib within the last 3 months
  6. Complete cytogenetic response on the last cytogenetic analysis within the last 12 months
  7. Major molecular remission without complete molecular remission
  8. ECOG grade 0 to 2
  9. SGOT et SGPT ≤ 2.5 N
  10. Bilirubin in serum ≤ 1.5 N
  11. Women of childbearing potential (WOCBP) must be using an adequate method of contraception

Exclusion Criteria:

  1. Participation in another clinical trial with any investigative drug within 30 days prior to study enrollment
  2. Prior history of hematopoietic stem cell transplantation (autologous or allogenic)
  3. Patient requiring anti-diabetic medication

  4. 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
  5. Grade III or IV fluid retention
  6. Known osteoporosis with therapy
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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France
CHR Annecy
Annecy, France
Institut Bergonié
Bordeaux, France
CH Versailles
Le Chesnay, France
CHU Lille
Lille, France
IPC
Marseille, France
CHU archet 1
Nice, France
St Louis
Paris, France
CHU Poitiers
Poitiers, France
CHU Purpan
Toulouse, France
Sponsors and Collaborators
Versailles Hospital
Investigators
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Principal Investigator: Rousselot Philippe, MD CH Versailles
More Information
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Responsible Party: Philippe ROUSSELOT, Study Coordinator, Versailles Hospital
ClinicalTrials.gov Identifier: NCT02888964    
Other Study ID Numbers: 09/37_ACTIM
First Posted: September 5, 2016    Key Record Dates
Last Update Posted: September 8, 2016
Last Verified: September 2016
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukemia
Neoplasms by Histologic Type
Neoplasms
 Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Chronic Disease
Disease Attributes
Pathologic Processes