VEN-R DASA-IPC 2022-067 Evaluation of DASATINIB monotherapy efficacy in acute myeloid leukemia patients refractory to VENETOCLAX-AZACITIDINE
- Conditions
- acute myeloid leukemiaTherapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-505846-24-00
- Lead Sponsor
- Institut Paoli-Calmettes
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 45
Confirmed diagnosis of AML except Philadelphia chromosome-positive AML (Ph+) and acute promyelocytic leukemia (AML M3), Age = 18 years, ECOG =3, VEN-AZA refractory defined as no response after two cycles of VEN-AZA whatever the dose and the treatment duration, Signed informed consent form, Affiliation to a social security system, or beneficiary of such a system
Central nervous system involvement, No efficient contraception for the women of childbearing age, Emergency situation person or not able to express his/her informed consent, Patient eligible to a targeted therapy having a market authorization, Patient under a legal protection measure (adult under guardianship, curatorship or safeguard of justice), Inability to undergo the clinical trial medical follow-up for geographical, social or psychological reasons, Heart failure defined as one of the following criteria: a. Stage III or IV heart failure according to the New York Heart Association Classification including pre-existing clinically significant arrhythmia, congestive heart failure or cardiomyopathy. b. Angina pectoris = 3 months before the start of the experimental treatment. c. Acute myocardial infarction = 3 months before the start of the experimental treatment. d. Other clinically significant heart disease (e.g. uncontrolled hypertension, history of labile hypertension or history of poor adherence with an antihypertensive medication). e. Left ventricle ejection fraction < 50 %., Liver failure defined as: a. Liver enzymes: ALT and/or AST = 2.5 of upper limit of normal except if the increased ALT/AST levels are related to AML. b. Total bilirubin = 3 x the upper limit of normal except in case of Gilbert’s syndrome., Kidney failure defined as creatinine clearance =45 ml/min (estimated by the diet in the renal disease equation or measured by using a 24-hour urine collection)., Contraindication to DASATINIB: a. Patients with a congenital long QT syndrome, patients treated with antiarrhythmic drugs or other medications that may cause long QT syndrome. b. Current therapy using strong inhibitors of CYP3A4 (ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, telithromycin, grapefruit juice). c. Patients with rare hereditary fructose intolerance, glucose-lactose malabsorption or sucrase-isomaltase deficiency., Positive for HIV, Hepatitis B or C, Pregnant or breastfeeding woman
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The main objective is to assess the tumor response after 2 cycles of DASATINIB monotherapy treatment for patients with chemotherapy-ineligible acute myeloid leukemia refractory to VEN-AZA therapy.;Secondary Objective: The secondary objectives are to assess the efficacy and tolerance of DASATINIB monotherapy treatment for patients with acute myeloid leukemia refractory to VENETOCLAX-AZACITIDINE therapy and to identify clinical and biological predictive factors of response to DASATINIB therapy.;Primary end point(s): Objective response rate after 2 cycles of 28 days DASATINIB defined as the rate of complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) according to ELN 2022 criteria.
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Different response rates (RC, CRi, or partial remission (PR)) according to ELN 2022 criteria.;Secondary end point(s):Blast clearance rate (morphologic leukemia free state, MLFS) according to ELN 2022 criteria;Secondary end point(s):Time to response (time between the start of the treatment until achievement of the CR, CRi or PR);Secondary end point(s):Duration of relapse-free period (time between the response time and the relapse);Secondary end point(s):Event-free survival (EFS, time between start of treatment and relapse, no reponse or death);Secondary end point(s):Overall survival (duration of survival from the start of the treatment);Secondary end point(s):Occurrence of Adverse Events according to CTCAE v5.0 and Serious Adverse Reaction