CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASE OR IN MYELOID BLAST CRISIS
Conditions
Interventions
Trade Name: PONATINIB
Product Name: Ponatinib
Pharmaceutical Form: Capsule
Sponsors
CENTRE HOSPITALIER DE VERSAILLES
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient aged 18y or more 2. Signed informed consent 3. Patient with Philadelphia chromosome positive CML in first blast crisis: CML-BP is defined by the presence of = 20% blasts in the bone marrow and/or peripheral blood or the presence of extramedullary disease. 4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3. 5. Have adequate renal function as defined by the following criterion: Serum creatinine = 1.5 × upper limit of normal (ULN) for institution 6. Have adequate hepatic function as defined by the following criteria: a- Total serum bilirubin = 1.5 × ULN, unless due to Gilbert’s syndrome or CML b- Alanine aminotransferase (ALT) = 2.5 × ULN, or = 5 × ULN unless related to the disease c- Aspartate aminotransferase (AST) = 2.5 × ULN, or = 5 × ULN unless related to the disease 7. Have normal pancreatic status as defined by the following criterion: Serum lipase and/or amylase = 1.5 × ULN 8. Have normal QTcF interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of = 450 ms in males or = 470 ms in females. 9. Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential). 10. Agree to use an effective form of contraception with sexual partners throughout study participation (for female and male patients who are fertile). 11. Have fully recovered (= grade 1, returned to baseline, or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study drug 12. Patient affiliated to or beneficiary of the French National Health service. 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 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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. Prior history of hematopoietic stem cell transplantation 4. 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 5. Individuals with another active malignancy 6. Patients at high risk or very high risk of arterio-veinous occlusive disease defined by European CVD score 7. Previously treated by 5-azacitidine or cytotoxic chemotherapy other than hydroxyurea 8. Diagnosis of malignant disease within the previous 12 months (excluding base cell carcinoma, "in-situ" carcinoma of the cervix or breast or other local malignancy excised or irradiated with a high probability of cure) 9. Known active viral infection with Human Immunodeficiency Virus (HIV) or Hepatitis type B or C 10. Are taking medications with a known risk of Torsades de Pointes. 11. Have active central nervous system (CNS) disease as evidenced by cytology or pathology. 12. Have uncontrolled hypertension (diastolic blood pressure > 90 mmHg; systolic > 150 mmHg). Patients with hypertension should be under treatment on study entry to affect blood pressure control. 13. Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the overall survival of patients with CML-AP (cohort A) and CML-BC (cohort-B) treated with the combination ponatinib and 5-azacitidine by 2 years;Secondary Objective: A.To determine the safety of selected therapies B.To assess the rate of CHR C.To assess the cytogenetic response D.To assess the molecular response E.To assess the rate of reversion to chronic phase CML F.To estimate the duration of response, event-free survival. G.To investigate the relationship between clinical efficacy and biological markers: mutations and methylation status. H.To estimate the rate of patients bridged to allogenic transplant I.To estimate survival after transplant and post-transplant relapse rate;Primary end point(s): Overall survival (OS) ;Timepoint(s) of evaluation of this end point: 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Adverse events - NCI-CTC Version 4.0 2. Cumulative rate of patients achieving CHR 3. Cumulative rate of patients achieving complete cytogenetic responses 4. Cumulative rate of patients achieving molecular responses 5. Cumulative rate of patients reverting to chronic phase CML 6. Analysis of clonal architecture, methylation profile, bcr-abl mutations and cytogenetics in blast crisis and AP at baseline, and in case of relapse or failure. 7. Event free survival, duration of response 8. Number of patients allocated to allogenic transplant 9. Survival after transplant and post-transplantation relapse rate;Timepoint(s) of evaluation of this end point: 2 years | — |
Countries
France
Contacts
Public ContactCharlotte LETERME - Project Manager
CENTRE HOSPITALIER DE VERSAILLES
Outcome results
None listed