Trial Information

Gemtuzumab Ozogamicin (GO) Combined With Standard Intensive Chemotherapy Versus Standard Intensive Chemotherapy Alone For Induction/Consolidation In Patients 61-75 Years Old With Previously Untreated AML: A Randomized Phase III Trial (AML-17) Of The EORTC-LG and the GIMEMA-ALWP

OBJECTIVES:

- Determine the antileukemic activity of standard induction chemotherapy with or without
gemtuzumab ozogamicin in elderly patients with previously untreated acute myeloid
leukemia.

- Determine the overall survival of patients treated with these regimens.

- Determine the rate of response, disease-free survival, event-free survival, incidence
of relapse, and incidence of death of patients treated with these regimens.

- Determine the rate, type, and grade of toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
according to age (61-69 vs 70-75), CD33 positivity (less than 5% vs 5-19% vs 20-80% vs more
than 80% vs unknown), initial WBC before hydroxyurea administration if needed (less than
30,000/mm^3 vs at least 30,000/mm^3), and participating center. Patients are randomized to 1
of 2 treatment arms.

- Arm I:

- Induction (phase I): Patients receive gemtuzumab ozogamicin IV over 2 hours on
days 1 and 15.

- Induction (phase II/MICE regimen): Beginning between days 50 and 53, patients
receive mitoxantrone IV over 30 minutes on days 1, 3, and 5; etoposide IV over 1
hour on days 1-3; and cytarabine IV continuously on days 1-7. Bone marrow
evaluation is performed on day 29. Patients with partial remission (PR) receive a
second course of MICE chemotherapy regimen. Patients with complete remission (CR)
after 1 or 2 courses of MICE regimen proceed to consolidation therapy. Patients
with progressive disease go off therapy.

- Consolidation: Beginning within 4 weeks of documentation of CR, patients receive
gemtuzumab ozogamicin IV over 2 hours on day 0; idarubicin IV on days 1, 3, and 5;
etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-5.
After at least day 30, patients receive a second consolidation course in the
absence of disease progression or unacceptable toxicity.

- Arm II:

- Induction (MICE regimen): Patients receive mitoxantrone, etoposide, and cytarabine
as in arm I induction. Bone marrow evaluation is performed on day 29. Patients
with PR receive a second course of MICE chemotherapy regimen. Patients with CR
after 1 or 2 courses of MICE regimen proceed to consolidation therapy. Patients
with progressive disease go off therapy.

- Consolidation: Patients receive idarubicin, etoposide, and cytarabine as in arm I
consolidation.

Patients are followed monthly for 1 year, every 3 months for 2 years, and then every 6
months thereafter.

PROJECTED ACCRUAL: A total of 450 patients (225 per treatment arm) will be accrued for this
study within 3.75 years.