Trial Information

RANDOMIZED PHASE III STUDY OF INDUCTION (ICE VS MICE VS DCE) AND INTENSIVE CONSOLIDATION (IDIA VS NOVIA VS DIA) FOLLOWED BY BONE MARROW TRANSPLANTATION IN ACUTE MYELOGENOUS LEUKEMIA: AML 10 PROTOCOL

OBJECTIVES: I. Determine the complete remission (CR) rate following 1 or 2 courses of ICE
(idarubicin/cytarabine/etoposide) vs. MICE (mitoxantrone/cytarabine/etoposide) vs. DCE
(daunorubicin/cytarabine/etoposide) in patients with newly diagnosed acute myeloid leukemia.
II. Compare disease-free survival and overall survival achieved with each anthracycline on
the above induction regimens and with intermediate-dose cytarabine (IDIA vs. NOVIA vs. DIA)
as consolidation therapy. III. Compare disease-free survival, relapse rate, death in first
CR, and overall survival in patients who receive peripheral blood stem cells (PBSC) vs.
autologous bone marrow transplant (AuBMT) vs. allogeneic bone marrow transplant (AlBMT) as
rescue from myeloablative therapy following remission consolidation. IV. Assess the time to
recovery of normal or acceptable polymorphonuclear leukocyte and platelet counts following
each treatment step. V. Determine the incidence and type of grade 4 toxicity and
treatment-related mortality. VI. Evaluate the quality of life during each step of treatment
using self-administered questionnaires. VII. Compare stem cell mobilization after IDIA vs.
NOVIA vs. DIA, each using granulocyte colony-stimulating factor as the mobilizing growth
factor. VIII. Assess the rate of completion of stem cell transplantation using PBSC vs.
AlBMT vs. AuBMT as the last step of therapy. IX. Compare the costs of treatment (e.g.,
antibiotics and transfusion requirements) and hospitalization duration between the AuBMT vs.
PBSC.

OUTLINE: Randomized study. All patients are randomized to Arms I, II, and III for
Induction/Consolidation. Patients in CR following Consolidation who have an HLA-identical
sibling, are less than 45 or 55 years of age (depending on center policy), and have adequate
organ function are nonrandomly assigned to AlBMT on Regimen A; those in CR who are without
an available sibling donor and who have adequate organ function proceed to Regimen B, then
are randomized to Arms IV and V. The following acronyms are used: AlBMT Allogeneic Bone
Marrow Transplant ARA-C Cytarabine, NSC-63878 AuBMT Autologous Bone Marrow Transplant BU
Busulfan, NSC-750 CTX Cyclophosphamide, NSC-26271 DCE DNR/ARA-C/VP-16 DHAD Mitoxantrone,
NSC-301739 DIA DNR/ID ARA-C DNR Daunorubicin, NSC-82151 G-CSF Granulocyte Colony-Stimulating
Factor (Rhone-Poulenc-Rorer) ICE IDA/ARA-C/VP-16 IDA Idarubicin, NSC-256439 ID Intermediate
Dose IDIA IDA/ID ARA-C Mesna Mercaptoethane sulfonate, NSC-113891 MICE DHAD/ARA-C/VP-16
NOVIA DHAD/ID ARA-C PBSC Peripheral Blood Stem Cells TBI Total-Body Irradiation VP-16
Etoposide, NSC-141540 INDUCTION/CONSOLIDATION: Arm I: 3-Drug Combination Chemotherapy
followed by 2-Drug Combination Chemotherapy. ICE; followed by IDIA. Arm II: 3-Drug
Combination Chemotherapy followed by 2-Drug Combination Chemotherapy. MICE; followed by
NOVIA. Arm III: 3-Drug Combination Chemotherapy followed by 2-Drug Combination Chemotherapy.
DCE; followed by DIA. POSTCONSOLIDATION THERAPY: Regimen A: Single-Agent Chemoablation plus
Radioablation or 2-Drug Chemoablation followed by Hematopoietic Rescue. CTX; plus TBI
(equipment unspecified); or CTX/BU; followed by AlBMT. Entry on EORTC study comparing CI IDA
with standard CTX/TBI or CTX/BU encouraged. Regimen B: Stem cell Mobilization and Harvest.
G-CSF or CTX/G-CSF. Arm IV: Single-Agent Chemoablation plus Radioablation or 2-Drug
Chemoablation followed by Hematopoietic Rescue. CTX/TBI or CTX/BU; followed by PBSC. Arm V:
Single-Agent Chemoablation plus Radioablation or 2-Drug Chemoablation followed by
Hematopoietic Rescue. CTX/TBI or CTX/BU; followed by AuBMT.

PROJECTED ACCRUAL: 1,520 patients will be randomized for Induction/Consolidation over about
5 years; if excessive deaths are found at interim analyses, the inferior arm will close. It
is expected that 744 patients will be randomized for Postconsolidation therapy, with 345
patients followed until relapse/death.