Trial Information

The Value of High Dose Versus Standard Dose ARA-C During Induction and of IL-2 After Intensive Consolidation/Autologous Stem Cell Transplantation in Patients (Age 15-60 Years) With Acute Myelogenous Leukemia. A Randomized Phase II Trial of the EORTC and the GIMEMA-ALWP

OBJECTIVES:

- Compare the overall survival rate in patients with acute myeloid leukemia treated with
high-dose versus standard-dose cytarabine during induction.

- Compare the disease-free survival rate in patients treated with or without
interleukin-2 following consolidation and autologous peripheral blood stem cell or bone
marrow transplantation.

- Compare the feasibility of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients in the first randomization are
stratified according to center, WBC (no greater than 25,000/mm^3 vs 25,000-99,000/mm^3 vs at
least 100,000/mm^3), age (15 to 45 vs 46 to 60), and performance status (0-1 vs 2 vs 3).
Patients in the second randomization are stratified according to center, first treatment arm
(I vs II), number of induction courses to reach complete remission (CR), cytogenic/molecular
genetic group at diagnosis (low vs high vs intermediate vs unknown), and autologous
peripheral blood stem cell (PBSC) transplantation planned after consolidation (yes vs no).

First randomization

- Induction: Patients are randomized to 1 of 2 treatment arms:

- Arm I: Patients receive standard-dose cytarabine IV over 24 hours on days 1-10,
etoposide IV over 1 hour on days 1-5, and daunorubicin IV over 5 minutes on days
1, 3, and 5.

- Arm II: Patients receive etoposide and daunorubicin as in arm I and high-dose
cytarabine IV over 3 hours every 12 hours on days 1, 3, 5, and 7.

- Consolidation: When CR is reached, patients receive intermediate-dose cytarabine IV
over 2 hours every 12 hours on days 1-6 and daunorubicin IV over 5 minutes prior to
cytarabine on days 4, 5, and 6.

- Harvest: Patients who achieve CR and are ineligible for allogeneic PBSC transplantation
receive filgrastim (G-CSF) subcutaneously (SQ) every 12 hours beginning 20 days after
starting consolidation treatment and continuing until autologous PBSC are harvested.
Autologous bone marrow is collected from patients with insufficient PBSC. Allogeneic
PBSC are harvested for patients who have an HLA identical donor. Allogeneic bone marrow
is harvested for high risk patients (under age 40) who have an unrelated bone marrow
donor.

- Transplant preparative chemotherapy: It is recommended that patients receive
cyclophosphamide on 2 consecutive days and total body irradiation on 3 days OR busulfan
on days -8, -7, -6, and -5 followed by cyclophosphamide on days -4 and -3.

- Transplantation: PBSC or bone marrow is infused on day 0.

Second randomization

- Patients who achieve CR with full hematologic recovery but have no HLA identical donor
are randomized to 1 of 2 treatment arms no earlier than day 22 after stem cell
infusion.

- Arm I: Patients receive interleukin-2 SQ once daily for 5 days. Treatment repeats
every 4 weeks for 1 year in the absence of disease progression or unacceptable
toxicity.

- Arm II: Patients receive no further treatment. Patients are followed at 1, 4, and
13 months, then every 4 months for 3 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 2,000 patients (1,000 per treatment arm) will be accrued for
the first randomization and a total of 577 patients (288 per treatment arm) will be accrued
for the second randomization of this study.