|- candidate number||1376|
|- NTR Number||NTR212|
|- Date ISRCTN created||20-dec-2005|
|- date ISRCTN requested||18-okt-2005|
|- Date Registered NTR||5-sep-2005|
|- Secondary IDs||HO43 |
|- Public Title||Randomized induction and post induction therapy in older patients (>= 61 yrs of age) with acute myelocytic leukemia (AML) and refractory anemia with excess of blasts (RAEB, RAEB-t).|
|- Scientific Title||Randomized induction and post induction therapy in older patients (>= 61 yrs of age) with acute myelocytic leukemia (AML) and refractory anemia with excess of blasts (RAEB, RAEB-t).|
|- ACRONYM||HOVON 43 AML / SAKK 30/01|
|- hypothesis||The first hypothesis to be tested is that the outcome in arm B is better than in arm A.
The second hypothesis to be tested is that the outcome in arm 2 is better than in arm 1.|
|- Healt Condition(s) or Problem(s) studied||Acute Myeloid Leukemia (AML)|
|- Inclusion criteria||1. Age 61 years or more;|
2. Subjects with a cytopathologically
confirmed diagnosis of AML (M0-M2 and M4-M7, FAB classification), or 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. Subjects with a secondary AML progressing from antecedent myelodysplasia and biphenotypic leukemia are eligible.
Antecedent MDS refers to any antecedent hematological disease of at least 4 month duration;
4. WHO performance status <= 2;
5. Written informed consent.
|- Exclusion criteria||1. Previous induction treatment for AML/MDS;|
2. Prior chemotherapy within 6 months of study entry;
3. Previous polycythemia rubra vera;
4. Primary myelofibrosis;
5. Blast crisis of chronic myeloid leukemia;
6. AML-FAB type M3 or AML with cytogenetic abnormality t(15;17);
7. Impaired hepatic or renal function as defined by:ALT and/or AST > 2.5 x normal valueBilirubin > 2 x normal value;
8. Serum creatinine > 2 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);
11. Unstable angina;
12. Unstable cardiac arrhythmias.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||9-okt-2000|
|- planned closingdate||1-nov-2005|
|- Target number of participants||800|
|- Interventions||Patients will be randomized on entry for induction between:|
Cycle I: conventional type daunomycin-cytarabine schedule;
Cycle II: intermediate dose cytarabine
Cycle I: daunomycin at escalated dose with standard dose cytarabine;
Cycle II: intermediate dose cytarabine.
Patients attaining CR and remaining in CR after cycle II will be randomized between:
Arm 1: no further treatment.
Arm 2: 3 dosages of gemtuzumab ozogamicin (GO, Mylotarg) at 4 week intervals.
For patients with an HLA identical sibling donor, an allograft with non-myeloablative conditioning, will be available depending on the active involvement in allotransplantation per center (optional per center).
|- Primary outcome||Endpoint for the comparison of induction treatment arm B with arm A:|
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 postinduction maintenance treatment with GO with no further treatment:
Disease-free survival measured from the date of second randomization to relapse or death from any cause.
|- Secondary outcome||Endpoints for the comparison of induction treatment arm B with arm A:|
1. Response and especially CR to chemotherapy cycles I and II;
2. Overall survival measured form 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. Probability of complete response, relapse, death in CR1, event-free survival, disease-free survival and overall survival will also be assessed in relation to age (61-70, 70-80, above 80), cytogenetic abnormalities, CD33-positivity of AML (phenotype), PgP positivity;
5. Toxicities and treatment related mortality;
6. Time to hematopoietic recovery (ANC 0.5 and 1.5 x 10^9/l; platelets 50 and 100 x 10^9/l) after each treatment cycle;
7. Number of platelet transfusions and last day of platelet transfusion after each cycle;
Endpoints for the comparison of postinduction maintenance treatment with GO with no further treatment:
8. Overall survival measured from the date of second randomisation;
9. Probability of relapse and death in first CR from date of second randomization calculated as competing risks;
10. Number and duration of hospitalization as well as transfusion requirements (red cell and platelet transfusion).
|- Trial web site||http://www.hovon.nl|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. B. L÷wenberg|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. B. L÷wenberg|
|- Sponsor/Initiator ||VU University Medical Center, Dutch haemato-oncology association (Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)|
(Source(s) of Monetary or Material Support)
|Koningin Wilhelmina Fonds (KWF)|
|- Brief summary||Study phase: |
evaluation of the effect of an escalated dose of Daunomycin in induction treatment. Evaluation of the effect of maintenance treatment with GO for patients in CR.
patients with AML except FAB M3 or t(15;17), RAEB or RAEB-t with IPSS >= 1.5, previously untreated, age >= 61 yrs.
prospective, multicenter, randomized with randomization up front for induction treatment and randomization of patients in CR for maintenance treatment or not.
Duration of treatment:
expected duration of 2 cycles of induction treatment inclusive evaluation is about 3 months. For patients in CR, randomized to GO, the additional treatment time is between 12 and 36 weeks.
|- Main changes (audit trail)|
|- RECORD||5-sep-2005 - 15-sep-2008|