PONATINIB for Chronic myeloid leukaemia in accelerated phase or myeloid blast crisis

Inclusion criteria

• {"criterion_text":"- Patient aged 18 years or more"}
• {"criterion_text":"- Signed informed consent"}
• {"criterion_text":"- Patient with Philadelphia chromosome positive CML in blast crisis: MBC-CML is defined by the presence of ≥ 20% blasts in the bone marrow and/or peripheral blood or the presence of extramedullary disease."}
• {"criterion_text":"- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3."}
• {"criterion_text":"- Have adequate renal function as defined by the following criterion: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) for institution"}
• {"criterion_text":"- Have adequate hepatic function as defined by the following criteria: a.\tTotal serum bilirubin ≤ 1.5 × ULN, unless due to Gilbert’s syndrome or CML / b.\tAlanine aminotransferase (ALT) ≤ 2.5 × ULN, or ≤ 5 × ULN unless related to the disease / c.\tAspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN unless related to the disease"}
• {"criterion_text":"- Have normal pancreatic status as defined by serum lipase and/or amylase ≤ 1.5 × ULN"}
• {"criterion_text":"- Have normal QTcF interval on screening electrocardiogram (ECG) evaluation, defined as QTcF of ≤ 450 ms in males or ≤ 470 ms in females."}
• {"criterion_text":"- Have a negative pregnancy test documented prior to enrolment (for females of childbearing potential)."}
• {"criterion_text":"- Agree to use an effective form of contraception with sexual partners throughout study participation (for female and male patients who are fertile)."}
• {"criterion_text":"- Have fully recovered (≤ grade 1, returned to baseline, or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study drug"}

Exclusion criteria

• {"criterion_text":"- Pregnant or lactating women"}
• {"criterion_text":"- Participation in another clinical trial with any investigative drug within 30 days prior to study enrolment"}
• {"criterion_text":"- Prior history of hematopoietic stem cell transplantation"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Individuals with another active malignancy"}
• {"criterion_text":"- Patients at high risk or very high risk of arterio-veinous occlusive disease defined by European CVD score ( appendix 9)"}
• {"criterion_text":"- Previously treated by 5-azacitidine or cytotoxic chemotherapy other than hydroxyurea"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Active viral infection with Human Immunodeficiency Virus (HIV) or Hepatitis type B or C"}
• {"criterion_text":"- Intake of medications with a known risk of Torsades de Pointes"}
• {"criterion_text":"- Have active central nervous system (CNS) disease as evidenced by cytology or pathology."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have any condition or illness that, in the opinion of the investigator, would compromise patient’s safety or interfere with the evaluation of the drug"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is Overall Survival by 2 years","definition_or_measurement_approach":"Determine the overall survival of patients with AP-CML (cohort A) and MBC-CML (cohort-B) treated with the combination of ponatinib and 5-azacitidine by 2 years."}

Secondary endpoints

• {"endpoint_text":"- Adverse events - CTCAE Version 4.0","definition_or_measurement_approach":"Adverse events assessed using CTCAE (NCI-CTC) Version 4.0."}
• {"endpoint_text":"- Cumulative rate of patients achieving CHR","definition_or_measurement_approach":"Cumulative incidence of patients achieving complete haematological response (CHR) as stated."}
• {"endpoint_text":"- Cumulative rate of patients achieving complete cytogenetic responses","definition_or_measurement_approach":"Cumulative incidence of patients achieving complete cytogenetic response as stated."}
• {"endpoint_text":"- Cumulative rate of patients achieving molecular responses","definition_or_measurement_approach":"Cumulative incidence of molecular responses as stated."}
• {"endpoint_text":"- Cumulative rate of patients reverting to chronic phase CML","definition_or_measurement_approach":"Cumulative incidence of patients reverting to chronic phase chronic myeloid leukaemia as stated."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Molecular and cytogenetic analyses (clonal architecture, methylation profile, BCR-ABL mutations and cytogenetics) performed at baseline and at relapse/failure as specified."}
• {"endpoint_text":"- Event free survival, duration of response","definition_or_measurement_approach":"Event-free survival and duration of response measured as stated (time-to-event endpoints)."}
• {"endpoint_text":"- Number of patients allocated to allogenic transplant","definition_or_measurement_approach":"Count of patients who proceed to allogeneic haematopoietic stem cell transplant."}
• {"endpoint_text":"- Survival after transplant and post-transplantation relapse rate","definition_or_measurement_approach":"Post-transplant survival and relapse rate measured after allogeneic transplant as stated."}

France

Earliest CTIS Part Ii Submission Date

15-07-2024

Latest Decision Or Authorization Date

05-01-2026

Processing Time Days

539

Number Of Sites

35

Number Of Participants

40

Primary sponsor

Full Name

Centre Hospitalier De Versailles

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"INCYTE","duties_or_roles":"Source of monetary support","organisation_type":""}