AML according to WHO classification (excluding acute promyelocytic leukaemia) or refractory anemia with excess of blasts (RAEB) and IPSS score =1.5 or therapy-related AML/RAEB or biphenotypic leukemia MedDRA version: 9.1 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia MedDRA version: 9.1 Level: LLT Classification code 10054593 Term: Refractory anemia with excess blasts in transformation
Conditions
Interventions
Product Name: Laromustine
Product Code: VNP40101M
Pharmaceutical Form: Solution for injection
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 18-65 years, inclusive Subjects with - a cytopathologically confirmed diagnosis of AML according WHO classification (excluding acute promyelocytic leukaemia) or - a diagnosis of refractory anemia with excess of blasts (RAEB) and IPSS score =1.5 or - patients with therapy-related AML/RAEB or - patients with biphenotypic leukemia (Appendices A1 and A2). WHO performance status 0, 1 or 2 (see Appendix I) Written informed consent 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: During part A of the study patients with a good risk AML, if already known at randomisation, will be excluded from randomisation and will be treated according to the control arm. Acute promyelocytic leukaemia Previous treatment for AML or RAEB, except hydroxyurea Impaired hepatic or renal function as defined by: ALT and/or AST > 3 x Upper Limit of Normal (ULN), or Bilirubin > 3 x ULN, or Serum creatinine> 3 x ULN (after adequate hydration), unless these are most likely caused by AML organ infiltration, Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etcetera), Cardiac dysfunction as defined by: - Myocardial infarction within the last 6 months of study entry, or - Reduced left ventricular function with an ejection fraction < 50% as measured by MUGA scan or echocardiogram (another method for measuring cardiac function is acceptable), or - Unstable angina, or - Unstable cardiac arrhythmias Pregnant or lactating females Impossibility to discontinue Disulfiram (Antabuse) and metronidazol (Flagyl 24 hours prior to study treatment. Unwillingness or not capable to use effective means of birth control
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For part A of the study: - To determine the feasibility of Laromustine when given at three possible dose levels together with standard induction cycles I and II in patients with AML/ RAEB with IPSS: =1.5 in a prospective comparison to standard induction cycles I and II without Laromustine For part B of the study: - To evaluate the effect of Laromustine at the selected feasible dose level when combined with remission induction chemotherapy cycles I and II as regards clinical outcome (“event-free survival”) in comparison to remission induction cycles I and II with no addition of Laromustine in a phase III study ;Secondary Objective: Part A of the study: To investigate of Laromustine in the combination with cytarabine-idarubicin remission induction therapy: the pharmacokinetics; the clinical efficacy with regard to complete remission rate at different dose levels of Laromustine Part B of the study: To investigate of Laromustine when combined with remission induction chemotherapy: the clinical efficacy with regard to the complete remission rate, disease free survival, risk of relapse and overall survival, the clinical efficacy in molecularly and cytogenetically distinguishable subsets with regard to the complete remission rate, disease free survival, risk of relapse and overall survival, the tolerance and toxicity See protocol for the other secondary endpoints ;Primary end point(s): For part A of the study: The assessment of Dose limiting toxicity and duration of myelosuppression of the combination of Laromustine at three selected dose levels. For part B of the study: Event-free survival (EFS) in relation to the induction treatment arms with and without Laromustine (i.e., time from registration to induction failure, death or relapse whichever occurs first). | — |
Countries
Belgium, Netherlands
Outcome results
None listed