Patients with Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), all risk scores, =65 years
Conditions
Interventions
Trade Name: Iclusig
Product Name: ponatinib
Pharmaceutical Form: Film-coated tablet
Sponsors
Centre Léon Bérard
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I1. Male or female patients aged =18 and =65 years at time of inform consent signature I2. Cytologically confirmed CML, Philadelphia chromosome positive with or without additional chromosomal abnormalities and/or BCR-ABL positive (Major BCR (M-BCR) transcript exclusively), i. e. Cryptic Philadelphia chromosome patients can be enrolled... I3. No prior treatment for CML with any tyrosine kinase inhibitor (eg. imatinib, dasatinib, nilotinib or bosutinib), or busulphan; interferon-alpha; homoharringtonine; cytosine arabinoside; or any other investigational agent; with the exception of hydroxyurea and/or anagrelide which are the only authorized prior treatments I4. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1 or 2 (Appendix 1) I5. Adequate organ functions as defined below according to lab tests performed within 7 days before Day 1... I6. Women of child-bearing potential must have a negative serum pregnancy test within 7 days before study drug start and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study treatments I7. Fertile men must agree to use an effective method of contraception during the study and for up to 3 months after the last dose of study treatments I8. Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol I9. Patients must be covered by a medical insurance 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: E1. Any form of prior auto- or allo-hemopoietic stem cell transplant E2. Hypersensitivity to the active substance or to any of the excipients of ponatinib and imatinib (see respective IB/SmPC) E3. Inability to take oral medication including malabsorption syndrome or other illness that could affect oral absorption of the study treatments (hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption) E4. Patients using, or requiring to use while on the study of any not permitted concomitant médications E5. Patients with a malignancy other than CP-CML within 5 years prior to Day 1 with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated in situ carcinoma of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal in situ carcinoma treated surgically with curative intent) E.6 Patients with active B or C hepatitis infection E.7 Patients with significant cardiovascular disease, such as New York Heart Association cardiac disease Class II or greater, myocardial infarction within 3 months prior to D1, unstable arrhythmias, unstable angina, peripheral arterial occlusive disease, brain stroke, heart stroke or evolutive ischemic cardiopathy, venous thromboembolism or pulmonary embolism; prolonged corrected QT interval (QTc) interval on baseline electrocardiogram (>450 msec on the Fridericia’s correction) despite correction of predisposants factors; long congenital QT syndrome E.8 Any of the following medical conditions despite adequate therapeutic management : ?- Uncontrolled HTA despite adequate ongoing treatment ?- Diabetes with documented target organ damage E9. Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the impact of ponatinib induction treatment on the rate of patients reaching the TFR criteria as defined by Rea et al. ;Secondary Objective: To further document the clinical activity of the proposed therapeutic strategy To document the safety of the proposed strategy To assess Ponatinib Pharmacokinetics over the 6-month of induction period To assess the impact of the proposed strategy on patients’ QoL To assess the patients’ compliance to the proposed therapeutic strategy ;Primary end point(s): Rate of patients reaching a stable MR4.5 (BCR-ABL (IS) =0.0032% with at least 32,000 copies of ABL) for = 2 years at Month 36 after initiation of ponatinib ;Timepoint(s) of evaluation of this end point: = 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Rate of patients with MR4.5 at 1, 2, 3, 6, 9, 12, 24 months after ponatinib initiation Rate of patients with MR4.0 at 1, 2, 3, 6, 9, 12, 24 months after ponatinib initiation Rate of patients with MMR at 1, 2, 3, 6, 9, 12, 24 and 36 months after ponatinib initiation Rate of patients with a BCR-ABL/ABL (IS) = 10% at 3 and 6 months after ponatinib initiation (EMR) Rate of patients with CCyR (or its molecular equivalent, BCR-ABL/ABL (IS) = 10%) at 3 and 6 months after ponatinib initiation Time to MR4.5, MR4.0 or MMR following ponatinib initiation Duration of MR4.5, MR4.0 or MMR Progression Free survival Overall survival For patients reaching TFR criteria and following imatinib cessation: Rate of successful TFR (patients sill with MR4.5) at 3, 6, 9, 12 and 24 months after imatinib cessation Duration of TFR after imatinib cessation OS, PFS after imatinib cessation Event-free survival according ELN recommendations20,21 Rate of TKI-withdrawal syndrome after Imatinib cessation25 Rate of MMR, MR4.0 and MR4.5 recovery in case of imatinib re-introduction Hematologic and non-hematologic AEs graded according to the NCI CTCAE v5.0 (Appendix 03) Incidence of arterial thrombotic events during the induction phase and during the consolidation phase Evolution of Quality of life according to QLQ-C30 and QLQ-CML24 questionnaires Plasma concentrations of ponatinib over the 6 months of the induction period Compliance to ponatinib and imatinib as evaluated using the Morisky medication adherence scale questionnaire ;Timepoint(s) of evaluation of this end point: Assessment troughout the study | — |
Countries
France
Contacts
Public ContactDRCI
Centre Léon Bérard
Outcome results
None listed