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).

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON21122

Enrollment

800

Registered

2005-09-05

Start date

2000-10-09

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute myelocytic leukemia, RAEB, RAEB-t.

Interventions

Patients will be randomized on entry for induction between: Arm A: Cycle I: conventional type daunomycin-cytarabine schedule

Cycle II: intermediate dose cytarabine Arm B: 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 (

Eligibility

Inclusion criteria

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

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.

Design outcomes

Primary

Measure	Time frame
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.	—

Measure

Time frame

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

Measure	Time frame
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).	—

Measure

Time frame

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).

—

Contacts

Public ContactB. Löwenberg

Erasmus Medical Center, Daniel den Hoed Cancer Center, Department of Hematology, P.O. Box 5201

b.lowenberg@erasmusmc.nl+31 (0)10 4391598

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)