RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known if combining combination chemotherapy with monoclonal antibody therapy will kill more cancer cells.

PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy with or without gemtuzumab ozogamicin in treating patients who have acute myeloid leukemia.

Condition	Treatment or Intervention	Phase
adult acute monoblastic and acute monocytic leukemia adult acute myeloid leukemia secondary acute myeloid leukemia	Drug: cytarabine  Drug: etoposide  Drug: gemtuzumab ozogamicin  Drug: idarubicin  Drug: mitoxantrone  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase III

Further Study Details: 

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.

• 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.
• 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.

Ages Eligible for Study:  61 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of acute myeloid leukemia (AML)
• Bone marrow blasts at least 20% by bone marrow aspiration or biopsy
• FAB subtypes M0-M2 and M4-M7
• No acute promyelocytic leukemia (FAB subtype M3)
• Previously untreated primary or secondary AML, including AML after myelodysplastic syndromes
• Hydroxyurea and/or corticosteroid therapy for no more than 14 days allowed
• No blast crisis of chronic myelogenous leukemia
• No AML supervening after other myeloproliferative diseases
• No active CNS leukemia

PATIENT CHARACTERISTICS: Age

• 61 to 75

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC less than 30,000/mm^3 (pretreatment with hydroxyurea for no more than 14 days allowed)

Hepatic

• Bilirubin no greater than 3 times upper limit of normal (ULN)

Renal

• Creatinine no greater than 3 times ULN

Cardiovascular

• No concurrent severe cardiovascular disease
• No arrhythmias requiring chronic treatment
• No congestive heart failure
• No symptomatic ischemic heart disease

Pulmonary

• No severe pulmonary dysfunction (CTC grade 3-4)

Other

• HIV negative
• No other uncontrolled infection
• No other concurrent malignant disease
• No severe concurrent neurological or psychiatric disease
• No prior alcohol abuse
• No psychological, familial, sociological, or geographical condition that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent hematopoietic growth factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) except for life-threatening infection due to neutropenia

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior enrollment in this trial

Belgium
      AZ Sint-Jan, Brugge,  8000,  Belgium; Recruiting
      Centre Hospitalier Peltzer-La Tourelle, VERVIERS,  B-4800,  Belgium; Recruiting
      Centre Hospitalier Universitaire Brugmann, Brussels,  B 1020,  Belgium; Recruiting
      CHU Liege - Domaine Universitaire du Sart Tilman, LIEGE,  B-4000,  Belgium; Recruiting
      Hopital de Jolimont, Haine-Saint-Paul,  7100,  Belgium; Recruiting
      Hopital Universitaire Erasme, Brussels,  1070,  Belgium; Recruiting
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium; Recruiting
France
      Centre Antoine Lacassagne, Nice,  06189,  France; Recruiting
      Hopital Edouard Herriot, Lyon,  69437,  France; Recruiting
      Hotel Dieu de Paris, Paris,  75181,  France; Recruiting
Germany
      Eberhard Karls Universitaet, Tuebingen,  D-72076,  Germany; Recruiting
      Klinikum der Albert - Ludwigs - Universitaet Freiburg, Freiburg,  D-79106,  Germany; Recruiting
      Ruprecht - Karls - Universitaet Heidelberg, Heidelberg,  D-69117,  Germany; Recruiting
Italy
      H. San Giovanni-Addolorata Hospital, Rome,  00184,  Italy; Recruiting
      Ospedale Sant' Eugenio, Rome,  00144,  Italy; Recruiting
Netherlands
      Jeroen Bosch Ziekenhuis, 's-Hertogenbosch,  5211 NL,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      Maxima Medisch Centrum - locatie Veldhoven, VELDHOVEN,  5500 MB,  Netherlands; Recruiting
      Nijmegen University Cancer Centre, Nijmegen,  6500 HB,  Netherlands; Recruiting
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands; Recruiting
Portugal
      Hospital Escolar San Joao, Porto,  4200,  Portugal; Recruiting

Study chairs or principal investigators

Sergio Amadori, MD,  Ospedale Sant' Eugenio   

Study ID Numbers:  CDR0000258151; EORTC-06012; AML-17; NCT00052299
Record last reviewed:  March 2005
Last Updated:  March 15, 2005
Record first received:  January 24, 2003
ClinicalTrials.gov Identifier:  NCT00052299
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08