PIO2STOP_Combination study of Pioglitazone and Tyrosine Kinase Inhibitors (TKIs) in Chronic Myeloid Leukemia patients after failure of a TKIs discontinuation attempt in order to prepare a new stop.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier De Versailles, Centre Hospitalier De Versailles

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

7 Nov 2016 → ongoing

Decision date (initial)

2024-10-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515460-31-00

EudraCT number

2016-002476-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To assess safety and pharmacokinetics of the combination of PIO and TKI in CML subjects who experience a loss of MMR following a TKI discontinuation. For patients included and eligible to discontinued, to assess survival without loss of MMR over a 12 months period following a subsequent TKI discontinuation.

Conditions and MedDRA coding

CHRONIC PHASE CHRONIC MYELOGENOUS LEUKAEMIA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. CML in any phase, patient in MR4.5
2. Loss of MMR following a first or subsequent TKI discontinuation trial.
3. Patient prior treated with imatinib, dasatinib, nilotinib, or bosutinib for more than 2 years from the last discontinuation
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 15

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety: To describe adverse events (AE) in subjects receiving the combination of PIO and TKI. AEs will be graded ac cording to the Common Terminology Criteria for Adverse Events (CTCAE) v.4.03 assessed through scheduled assessment and subject reported diary. To evaluate the pharmacokinetic parameters of pioglitazone and TKIs.
2. Efficacy : To determine the proportion of subjects who maintain MMR over a 12 months period following discontinuation of PIO and TKI using blood qRT-PCR for BCR-ABL1 obtained monthly for the first 6 months, quarterly following 6 months, and bi-annually the second year, thereafter , in accordance of the center policy.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier De Versailles

Sponsor organisation

Centre Hospitalier De Versailles

Address

177 Rue De Versailles, Le Chesnay Le Chesnay

City

Le Chesnay Rocquencourt

Postcode

78150

Country

France

Scientific contact point

Organisation

Centre Hospitalier De Versailles

Contact name

Project Manager

Public contact point

Organisation

Centre Hospitalier De Versailles

Contact name

Project Manager

Centre Hospitalier De Versailles

Sponsor organisation

Centre Hospitalier De Versailles

Address

177 Rue De Versailles, Le Chesnay Le Chesnay

City

Le Chesnay Rocquencourt

Postcode

78150

Country

France

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications