Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Acute Myelogenous Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 15 to 60 EORTC-06931 NCT00002549

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.

Entry Criteria

Disease Characteristics:

Newly diagnosed acute myeloid leukemia (AML) of any FAB histology (M1-M7)
except M3
  At least 30% blast cells in bone marrow smears

Secondary leukemias eligible, as follows:
  Following cured malignancies, including Hodgkin's disease
  Following exposure to alkylating agents or radiotherapy for other reasons

The following leukemias are excluded:
  Blast crisis of chronic myeloid leukemia
  Leukemia secondary to other myeloproliferative disease
  Leukemia secondary to myelodysplastic syndrome of more than 6 months'
     duration

No other progressive malignant disease

Prior/Concurrent Therapy:

No prior therapy for AML (chemotherapy, radiotherapy, or more than 7 days of
corticosteroids)

Patient Characteristics:

Age:
  15 to 60

Performance status:
  Not specified

Hematopoietic:
  Not applicable

Hepatic:
  Bilirubin no greater than 1.5 x ULN

Renal:
  Creatinine no greater than 1.5 x ULN

Cardiovascular:
  No severe heart failure requiring diuretics or with an LVEF less than 50%

Other:
  No severe concomitant neurologic disease
  No severe concomitant psychologic disease

Expected Enrollment

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.

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.

Oosterveld, M, Suciu S, Muus P, et al.: A new prognostic disease specific model to predict survival after intensive antileukemic treatment for young patients with poor-risk MDS and AML: results of the CRIANT and AML-10 studies conducted by the EORTC/GIMEMA/SAKK/HOVON/EBMT groups. [Abstract] Blood 104 (11): A-2020, 2004.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Robert A. Zittoun, MD, Protocol chair(Contact information may not be current)		Ph: 33-1-42-348-413

Registry Information
Official Title		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
Trial Start Date		1993-11-17
Registered in ClinicalTrials.gov		NCT00002549
Date Submitted to PDQ		1993-11-17
Information Last Verified		2007-05-04