CHRONIC PHASE CHRONIC MYELOGENOUS LEUKAEMIA (CP-CML) MedDRA version: 19.0 Level: LLT Classification code 10058246 Term: Chronic myelogenous leukaemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: ACTOS
Pharmaceutical Form: Tablet
Sponsors
Centre Hospitalier de Versailles
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: These inclusion criteria will apply for all arms. Specific criteria may apply for each experimental arm. 1. Patient aged 18y or more 2. Signed informed consent 3. Patient with Philadelphia chromosome positive chronic phase CML and M BCR-ABL1 transcript positivity 4. Treatment with imatinib, nilotinib, dasatinib, bosutinib or ponatinib for more than 2 years overall 5. No switch between tyrosine kinase inhibitors within the last 3 months 6. No dose modification within the last 3 months 7. Complete cytogenetic response or BCR-ABLIS = 1% 8. Detectable BCR-ABL1 with BCR-ABLIS > 0.0032% (less than MR4.5) 9. ECOG grade 0 to 2 10. ASAT and ALAT = 2.5 N 11. Bilirubin in serum = 2.5 N 12. Women of childbearing potential must be using an adequate method of contraception Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women, 2. Participation in another clinical trial with any investigative drug within 30 days prior to study enrolment, 3. Patient requiring anti-diabetic medication 4. Prior history of hematopoietic stem cell transplantation (autologous or allogenic) 5. Cardiovascular disease: • Stage II 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 6. Grade III or IV fluid retention 7. Known BCR-ABL kinase domain mutation 8. CML patient not in chronic phase at diagnosis 9. Individuals with an active malignancy 10. Kown HIV-positivity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To select molecules in combination or sequentially with imatinib, nilotinib, dasatinib, bosutinib or ponatinib potentially able to produce a 25% increase in the Cumulative Incidence of MR4.5 as compare to control. ;Secondary Objective: A.To determine the safety of selected therapies B.To determine the rate of MR4 by 12, 24, 36, 48 months in experimental and control arms C.To determine the rates of MR4.5 by 24, 36, 48 months in experimental and control arms D.To determine the rate of undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 12, 24, 36, 48 months in experimental and control arms E.To estimate treatment free remission (TFR) in patients eligible for discontinuation studies F.To investigate the relationship between biological activity and the clinical efficacy of the selected therapies G.To assess the effects of the treatments on the number and clonogenicity of CML stem cells and other biological markers of interest H.To estimate duration of response, progression-free survival, event free survival and overall survival. ;Primary end point(s): The primary end-point is the cumulative incidence of patients achieving a deep molecular response defined by MR4.5 or deeper (BCR-ABLIS = 0.0032 %) by 12 months.;Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Adverse events 2. The cumulative rate of patients achieving MR4.5 by 24, 36, 48 months in experimental and control arms 3. The cumulative rate of patients achieving MR4 by 12, 24, 36, 48 months in experimental and control arms 4. The cumulative rate of patients with undetectable BCR-ABL1 transcript (sensitivity 40000 ABL copies) by 12, 24, 36, 48 months in experimental and control arms 5. The rate of patients in treatment free remission during follow-up 6. Measurement of number and clonogenicity of CML stem cells using the leukemic stem cell markers followed by flow cytometry analysis and the LTC-IC assay and others markers (ancillary study) 7. Survival, progression free survival, event free survival, duration of response ;Timepoint(s) of evaluation of this end point: 12, 24, 36, 48 months | — |
Countries
France
Contacts
Public Contactcoordinatrice DRCI
Centre Hospitalier de Versailles
Outcome results
None listed