Clinical trial NCT02889003: Second STOP After Pioglitazone Priming in CML Patients
Official title: Combination Study of Pioglitazone and Tyrosine Kinase Inhibitors (TKIs) in Chronic Myeloid Leukemia Patients After Failure of a First TKIs Discontinuation Attempt in Order to Prepare a New Stop
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia (CML)
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
Collaborators: name: Pr Philippe ROUSSELOT
First posted: 2016-09-05
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Single-center study, prospective, phase II trial.

The study objectives are :

* To assess safety and pharmacokinetics of the combination of PIO and TKI in CML subjects who experience a loss of MMR following a first TKI discontinuation.
* To assess survival without loss of MMR over a 12 months period following a second TKI discontinuation in subjects who achieve or maintain \< MR4.5 with the combination PIO and TKI administered for at least 6 months.


Eligibility criteria: Inclusion Criteria:

1. CML in any phase. patient in MR4
2. Loss of MMR following a first or subsequent TKI discontinuation trial.
3. Patient prior treated with imatinib, dasatinib, nilotinib, or bosutinib
4. Age \>18 years.
5. Serum bilirubin \<1.5 x upper limit of normal values.
6. AST (SGOT)/ALT (SGPT) \<2.5x upper limit of normal values.
7. Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative urine pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device, transdermal/implanted or injected contraceptives and abstinence.
8. Males must agree to abstain from sexual activity or agree to utilize a medically-approved contraception method during and for 3 months after the treatment period.
9. Signed informed consent.
10. Be able and willing to comply with study visits and procedures

Exclusion Criteria:

1. Known loss of CCyR by marrow cytogenetic or blood FISH for BCR-ABL1.
2. Loss of CHR.
3. Participation in another clinical trial with any investigative drug within 30 days prior to study enrolment.
4. Prior allogeneic hematopoietic stem cell transplantation.
5. Patient requiring anti-diabetic medications to manage hyperglycemia.
6. Cardiovascular disease: history of congestive heart failure, myocardial infarction within the 6 months of study entry, symptomatic cardiac arrhythmia requiring treatment.
7. Hepatic insufficiency
8. History of bladder cancer.
9. Diagnosed hematuria.
10. Known osteoporosis with curative therapy (prophylactic therapy is not an exclusion criteria)
11. Known history of macular edema.
12. Known history of ABL1-domain mutation associated with resistance to the discontinued TKI.
13. Known allergy to PIO.
14. Pregnant or breastfeeding.
15. Use of TZD within 28 days prior to enrollment.
16. Significant gastrointestinal condition that could potentially impair the absorption or disposition of the drug.
17. Uncontrolled peripheral edema (2+ or more) of any etiology

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Up to 24 months after inclusion
measure: Treatment free survival after pioglitazone and tyrosine kinase inhibitor discontinuation.
timeFrame: Up to 24 months after inclusion
Secondary outcomes:
Other outcomes:
Locations:
city: Le Chesnay
country: France
facility: Centre Hospitalier de Versailles
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
city: Nantes
country: France
facility: CHU de Nantes
city: Rennes
country: France
facility: CHU de Rennes
Study officials:
References: