Acute Myeloid leukemia (AML), RAEB
Conditions
Interventions
Patients will be randomized on entry for induction between:
Arm A:
Cycle I: idarubicin and conventional dose cytarabine
Cycle II: amsacrine and intermediate dose cytarabine
Arm B:
Cycle I: id
Sponsors
Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age 18-65 years, inclusive 2. 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). 3. WHO performance status 0, 1 or 2 (see Appendix I) 4. Written informed consent
Exclusion criteria
Exclusion criteria: 1. During part A of the study patients with a good risk AML, if already known at randomisation. These patients will be treated outside the study according to the control arm. 2. Acute promyelocytic leukaemia 3. Previous treatment for AML or RAEB, except hydroxyurea 4. 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, 5. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etcetera), 6. 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 7. Pregnant or lactating females 8. Impossibility to stop Disulfiram (Antabuse) and metronidazol (Flagyl) 24 hours prior to study treatment. (Please note that this medication must be stopped 24 hours prior to study treatment.) 9. Unwilling or not capable to use effective means of birth control
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: The assessment of DLT and duration of myelosuppression of the combination of Laromustine at three selected dose levels. Part B: 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). | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: The evaluation of Laromustine and cytarabine pharmacokinetics.Response and especially CR to chemotherapy cycles I and II Part B: 1) EFS in the distinct prognostic subsets (AML good-risk vs AML intermediate-risk vs AML poor-risk) and cytogenetically and molecularly defined subgroups. 2) Response and especially CR to chemotherapy cycles I and II 3) Overall survival (OS) measured from the time of registration 4) Disease-free interval (duration of the first CR) measured from the time of achievement of CR to day of relapse or death from any cause (whichever occurs first). 5) Outcome of induction treatments in relation to minimal residual disease measurements 6) Evaluation of Laromustine and cytarabine (Ara-C) pharmacokinetics 7) Evaluation of the effect of Laromustine on peripheral CD34 cell numbers collected for autologous peripheral blood transplantation 8) Evaluation of molecular prognostic markers and gene expression profiles for outcome in relation to induction and postinduction treatments 9) Evaluation of toxicities and treatment related mortality (according to Appendix H) 10) Time to hematopoietic recovery (ANC 0.5 and 1.0 x 10^9/L; platelets 50 and 100 x 10^9/L) after each treatment cycle 11) Number of platelet transfusions and last day of platelet transfusion after each cycle. | — |
Contacts
Public ContactB. Löwenberg
Erasmus Medical Center, Daniel den Hoed Cancer Center, Department of Hematology, P.O. Box 5201
Outcome results
None listed