RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. 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. Giving monoclonal antibody therapy together with chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together with gemtuzumab ozogamicin works in treating patients with previously untreated high-risk myelodysplastic syndrome or acute myeloid leukemia secondary to myelodysplastic syndrome.

Condition	Treatment or Intervention	Phase
adult acute myeloid leukemia Chronic Myelomonocytic Leukemia Myelodysplastic Syndromes	Drug: busulfan  Drug: cyclophosphamide  Drug: cytarabine  Drug: gemtuzumab ozogamicin  Drug: idarubicin  Procedure: allogeneic bone marrow transplantation  Procedure: antibody conjugate therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: bone marrow transplantation  Procedure: chemotherapy  Procedure: monoclonal antibody therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the feasibility of combining gemtuzumab ozogamicin with idarubicin and cytarabine with or without cyclophosphamide with total body irradiation vs busulfan followed by allogeneic stem cell transplantation in patients with previously untreated high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia secondary to MDS.
• Determine the toxicity profile of this regimen in these patients.
• Determine the antileukemic/anti-MDS activity of this regimen in these patients.

Secondary

• Determine the hepatotoxicity of this regimen, in terms of veno-occlusive disease, in these patients.
• Determine the severity of pancytopenia and duration of recovery in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups.

• Group 1 (for patients with no HLA-matched sibling donor): Patients receive remission-induction chemotherapy comprising idarubicin IV over 5 minutes on days 1, 3, and 5; cytarabine IV continuously over 24 hours on days 1-10; and gemtuzumab ozogamicin IV over 2 hours on day 7. Treatment continues for a second course in the absence of unacceptable toxicity.
• Patients are randomized to 1 of 2 treatment arms.
• Arm I: Patients receive myeloablative consolidation chemotherapy comprising cyclophosphamide on days -6 and -5 and total body irradiation twice daily on days -4 to -2.
• Patients receive myeloablative consolidation chemotherapy comprising busulfan on days -8 to -5 and cyclophosphamide on days -4 and -3. Patients in both arms may alternatively undergo T-cell depletion and/or a reduced-intensity conditioning regimen.

Approximately 4-8 weeks after completion of consolidation chemotherapy, all patients in group 2 undergo allogeneic bone marrow transplantation or allogeneic peripheral blood stem cell transplantation. Patients in group 2 then proceed to remission-induction chemotherapy as in group 1.

Patients achieving complete remission are recommended for consolidation therapy off study.

Patients are followed monthly for 6 months, every 2 months for 6 months, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study within 10 months.

Ages Eligible for Study:  16 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:
• High-risk myelodysplastic syndromes (MDS), including any of the following:
• Refractory anemia with excess blasts (RAEB) with > 10% blast cells in the bone marrow
• RAEB in transformation
• Other forms of MDS with multiple (3 or more) chromosomal abnormalities or chromosome 7 abnormalities AND/OR profound cytopenias, defined as neutrophil count < 500/mm^3 and/or platelet count < 20,000/mm^3
• Chronic myelomonocytic leukemia with > 5% blast cells in the bone marrow
• Chronic myelomonocytic leukemia with neutrophil count > 16,000/mm^3 OR monocyte count > 2,600/mm^3
• Secondary acute myeloid leukemia supervening after overt MDS of more than 6 months in duration
• Patients with or without an HLA-identical sibling
• No active CNS leukemia

PATIENT CHARACTERISTICS: Age

• 16 to 70

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

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

Pulmonary

• No severe lung disease

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No HIV positivity
• No other concurrent malignant disease
• No active uncontrolled infection
• No history of alcohol abuse (i.e., averaged less than 5 alcoholic consumptions daily for the past year)
• No concurrent severe neurological or psychiatric disease
• No other psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 6 weeks since prior growth factors

Chemotherapy

• No prior intensive chemotherapy
• More than 6 weeks since prior low-dose chemotherapy or hydroxyurea

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 6 weeks since prior immunosuppressants
• No prior participation in this clinical study

Belgium
      AZ Sint-Jan, Brugge,  8000,  Belgium; Recruiting
      Cliniques Universitaires Saint-Luc, Brussels,  1200,  Belgium; Recruiting
      H. Hartziekenhuis V.Z.W., Roeselare,  8800,  Belgium; Recruiting
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
Germany
      Ruprecht - Karls - Universitaet Heidelberg, Heidelberg,  D-69117,  Germany; Recruiting
Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      Onze Lieve Vrouwe Gasthuis, Amsterdam,  1091 HA,  Netherlands; Recruiting
      University Medical Center Nijmegen, Nijmegen,  NL-6500 HB,  Netherlands; Recruiting
Switzerland
      Universitatsspital-Basel, Basel,  CH-4031,  Switzerland; Recruiting

Study chairs or principal investigators

Theo De Witte, MD, PhD,  University Medical Center Nijmegen   

Study ID Numbers:  CDR0000349501; EORTC-06013; NCT00077116
Record last reviewed:  March 2005
Last Updated:  April 5, 2005
Record first received:  February 10, 2004
ClinicalTrials.gov Identifier:  NCT00077116
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08