RATIONALE: Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy uses different ways to stop cancer cells from dividing so they stop growing or die. Combining gemtuzumab ozogamicin with chemotherapy may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of gemtuzumab ozogamicin with or without chemotherapy in treating older patients who have acute myeloid leukemia.

Condition	Treatment or Intervention	Phase
untreated adult acute myeloid leukemia adult acute differentiated monocytic leukemia (M5b) adult acute myeloblastic leukemia without maturation (M1) adult acute minimally differentiated myeloid leukemia (M0) adult acute poorly differentiated monocytic leukemia (M5a) adult acute erythroleukemia (M6) adult acute myelomonocytic leukemia (M4) adult acute myeloblastic leukemia with maturation (M2) secondary acute myeloid leukemia adult acute megakaryocytic leukemia (M7)	Drug: cytarabine  Drug: etoposide  Drug: gemtuzumab ozogamicin  Drug: idarubicin  Drug: mitoxantrone	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the feasibility, toxicity, and antileukemic activity of gemtuzumab ozogamicin (CMA-676) with or without mitoxantrone, etoposide, cytarabine, and idarubicin in elderly patients with acute myeloid leukemia.

PROTOCOL OUTLINE: This is a multicenter study. Patients are stratified according to risk (standard risk, defined as age 61-75 and WHO performance status 0-1 vs poor risk, defined as over 75 years and WHO performance status 0-2 OR under 76 years and WHO performance status 2). Frontline therapy: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Stratum I (Standard risk patients): Patients with disease progression at any time during frontline therapy may begin induction therapy immediately. Induction therapy begins 7-10 days after response assessment regardless of response and in the absence of unacceptable toxicity. Stratum II (Poor risk patients): Patients experiencing complete remission with or without platelet recovery will begin consolidation therapy within 4-8 weeks of response assessment in the absence of unacceptable toxicity. Stratum I Induction therapy: 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. Patients experiencing partial response are given a second induction therapy course. Patients experiencing complete remission with or without platelet recovery after 1 or 2 induction courses begin consolidation therapy within 4-8 weeks of response assessment in the absence of unacceptable toxicity. Consolidation therapy: Patients receive 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. Stratum II Consolidation therapy: Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and then 1-3 months later. Patients are followed monthly for 1 year, every 3 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 45-82 (28-49 for stratum I, and 17-33 for stratum II) patients will be accrued for this study.

Ages Eligible for Study:  61 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of primary or secondary acute myeloid leukemia (AML); Previously untreated; At least 20% marrow blasts AML after myelodysplastic syndrome allowed; No leukemia after other myeloproliferative diseases; No acute promyelocytic leukemia (M3) or blastic phase chronic myelogenous leukemia
• No active CNS leukemia

--Prior/Concurrent Therapy--

• Biologic therapy: No prior humanized monoclonal antibody therapy
• Chemotherapy: Up to 7 days of prior hydroxyurea allowed; At least 24 hours since prior hydroxyurea; No other prior chemotherapy for AML
• Endocrine therapy: No more than 7 days of prior corticosteroids; No other prior endocrine therapy
• Radiotherapy: No prior radiotherapy
• Surgery: Not specified

--Patient Characteristics--

• Age: 61 and over
• Performance status: WHO 0-2
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics; White blood count no greater than 30,000/mm3 unless reducible to less than 30,000/mm3 by a maximum of 7 days of hydroxyurea
• Hepatic: Bilirubin no greater than 3 times upper limit of normal (ULN)
• Renal: Creatinine no greater than 3 times ULN
• Cardiovascular: No severe heart failure that would preclude study
• Pulmonary: No severe lung failure that would preclude study
• Other: No other concurrent malignancies; No active uncontrolled infection; No concurrent severe neurological or psychiatric disease; No psychological, familial, sociological or geographical condition that would preclude compliance with study; HIV negative

Austria
      Innsbruck Universitaetsklinik, Innsbruck,  A-6020,  Austria
Belgium
      A.Z. St. Jan, Brugge,  8000,  Belgium
      CHU Sart-Tilman, LIEGE,  B-4000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Croatia
      University Hospital Rebro, Zagreb,  41000,  Croatia
France
      Hopital Edouard Herriot, Lyon,  69437,  France
      Hopital Necker, Paris,  75743,  France
      Hotel Dieu de Paris, Paris,  75181,  France
Germany
      Eberhard Karls Universitaet, Tuebingen,  D-72076,  Germany
      Medizinische Klinik und Poliklinik, Heidelberg,  D-69115,  Germany
Italy
      Azienda Policlinico Umberto Primo, Rome,  00161,  Italy
      Ospedale Generale Regionale, Bolzano,  39100,  Italy
      Ospedale San Eugenio, Rome,  00144,  Italy
      Ospedali Riuniti, Reggio Calabria,  89100,  Italy
      Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore, Rome,  00168,  Italy
Netherlands
      Groot Ziekengasthuis 's-Hertogenbosch, 's-Hertogenbosch,  5211 NL,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands

Study chairs or principal investigators

Sergio Amadori,  Study Chair,  EORTC Leukemia Cooperative Group   

Study ID Numbers:  CDR0000068137; EORTC-06993-AML-15
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006122
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08