Acute myelocytic leukemia, RAEB, RAEB-t.
Conditions
Interventions
Patients will be randomized on entry for induction between:
Arm A:
1. Cycle I: idarubicin and conventional dose cytarabine
2. Cycle II: amsacrine and intermediate dose cytarabine
Arm B:
1. Cycle I: idarubicin and intermediate dose cytarabine
2. Cycle II: amsacrine and high dose cytarabine
A second randomization for induction will involve yes or no priming with G-CSF during chemotherapy of induction cycles I and II.
All CR patients will be distinguished according to good risk, interme
2. Arm 2: busulfan-cyclophosphamide ablation + autologous PBSCT.
Patients who are not elig
Sponsors
Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)
P/a HOVON Data Center
Erasmus MC - Daniel den Hoed
Postbus 5201
3008 AE Rotterdam
Tel: 010 4391568
Fax: 010 4391028
e-mail: hdc@erasmusmc.nl
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age 18-60 years (incl.); 2. Subjects with a cytopathologically. confirmed diagnosis of (a)AML (M0-M2 and M4-M7, FAB classification), or (b) with refractory anemia with excess of blasts (RAEB) or refractory anemia with excess of blasts in transformation (RAEB-t) with an IPSS score of >=1.5; 3. Patients with therapy-related AML/RAEB/RAEB-t are eligible provided they have not received chemotherapy during the past 6 months. Also patients with biphenotypic leukemia may be included; 4. Subjects with a secondary AML progressing from antecedent myelodysplasia are eligible. Antecedent MDS refers to a condition of at least 4 month duration; 5. WHO performance status <= 2; 6. Written informed consent.
Exclusion criteria
Exclusion criteria: 1. Prior chemotherapy within 6 months of study entry; 2. Relapse of AML or MDS after induction chemotherapy; 3. Prior stem cell transplant; 4. Previous polycythemia rubra vera; 5. Primary myelofibrosis; 6. Blast crisis of chronic myeloid leukemia; 7. AML-FAB type M3 or AML with cytogenetic abnormality t(15;17) or AML with a PML/RAR alpha or a variant RAR alpha fusion gene; 8. Impaired hepatic or renal function as defined by: ALT and/or AST > 3 x normal value, Bilirubin > 3 x normal value, Serum creatinine > 3 x normal value (after adequate hydration), (unless these are most likely caused by AML organ infiltration); 9. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, etc.); 10. 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), unstable angina, unstable cardiac arrhythmias; 11. Pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Endpoint for the comparison of induction treatment arm B with arm A and for the comparison yes or no G-CSF priming: 1. Event-free survival (i.e., time from registration to induction failure, death or relapse whichever occurs first); the time to failure of patients with induction failure is set at one day. Endpoint for the comparison of PBSCT with cycle III: 1. Disease-free survival measured from the date of second randomization to relapse or death from any cause. Endpoint for the evaluation of Allo SCT: 1. Disease-free survival measured from the date of Allo SCT to relapse or death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Endpoints for the comparison of induction treatment arm B with arm A and for the comparison yes or no G-CSF priming: 1. Response and especially CR to chemotherapy cycles I and II. 2. Overall survival measured from the time of registration. 3. 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). 4. Toxicities and treatment related mortality. 5. Time to hematopoietic recovery (ANC 0.5 and 1.5 x 109/l; platelets 50 and 100 x 109/l) after each treatment cycle. 6. Number of platelet transfusions and last day of platelet transfusion after each cycle. Endpoints for the comparison of PBSCT with cycle III: 1. Overall survival measured from the date of second randomization. 2. Probability of relapse and death in first CR from date of second randomization calculated as competing risks. 3. Duration of hospitalization as well as transfusion requirements (red cell and platelet transfusion). 4. Time to hematopoietic recovery. Endpoints for the evaluation of Allo SCT: 1. Overall survival measured from the date of Allo SCT. 2. Probability of relapse and death in first CR from date of second randomization calculated as competing risks. 3. Duration of hospitalization as well as transfusion requirements (red cell and platelet transfusions). 4. Time to hematopoietic recovery. 5. Incidence and severity of acute and chronic GvHD. | — |
Contacts
Public ContactB. Löwenberg
Erasmus Medical Center, Daniel den Hoed Cancer Center, Department of Hematology, P.O. Box 5201
Outcome results
None listed