Randomised Induction and Post Induction Therapy in Older Patients (≥61 Years of Age) With Acute Myeloid Leukemia (AML) and Refractory Anemia With Excess Blasts (RAEB, RAEB-t)
- Compare the event-free and disease-free survival of older patients with acute myeloid
leukemia, refractory anemia with excess blasts (RAEB), or RAEB in transformation
treated with induction therapy comprising cytarabine in combination with two different
doses of daunorubicin followed by cytarabine alone with or without post-induction
therapy comprising gemtuzumab ozogamicin.
- Compare the complete remission rate in patients treated with these regimens.
- Compare the overall survival of patients treated with these regimens.
- Compare the toxicity of these regimens in these patients.
- Determine the probability of relapse and death during first complete remission in
patients treated with post-induction gemtuzumab ozogamicin.
- Correlate prognostic factors (e.g., CD33 positivity, multidrug resistance phenotype, or
cytogenetics) with probability of complete remission and overall, event-free, and
disease-free survival of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
participating center and diagnosis (acute myeloid leukemia [AML] vs myelodysplastic
syndromes [MDS]) for induction therapy. Patients are stratified according to participating
center, diagnosis (AML vs MDS), induction treatment arm (I vs II), and response to induction
therapy (complete remission [CR] vs no CR) for post-induction therapy.
- Induction therapy (course 1): Patients are randomized to 1 of 2 induction treatment
- Arm I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV
over 3 hours on days 1-3.
- Arm II: Patients receive cytarabine as in arm I and daunorubicin as in arm I but
at a higher dose.
Approximately 28-35 days after the start of course 1 (or sooner if the bone marrow shows
evidence of resistant disease), patients in both arms proceed to course 2 of induction
- Induction therapy (course 2): All patients receive cytarabine IV over 6 hours twice
daily on days 1-6.
After completion of course 2, patients undergo assessment of remission status. Patients who
do not achieve CR are removed from the study. Patients achieving CR proceed to
post-induction therapy and undergo a second randomization.
- Post-induction therapy: Patients are randomized to 1 of 2 post-induction treatment
- Arm I: Patients receive no further chemotherapy.
- Arm II: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1, 29, and
57 in the absence of disease relapse or unacceptable toxicity.
After completion of study treatment, patients are followed monthly for 1 year, every 3
months for 2 years, every 4-6 months for 2 years, and then periodically thereafter.
PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 4-5 years.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Event-free survival after induction therapy
Jonathan Kell, MRCPath
The University of New South Wales
Netherlands: Independent Ethics Committee