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

Alternate Title

Idarubicin, Cytarabine, and Gemtuzumab Ozogamicin in Treating Patients With Previously Untreated High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia Secondary to Myelodysplastic Syndrome

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	16 to 70	Other	EORTC-06013 NCT00077116

Objectives

Primary

1. 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.
2. Determine the toxicity profile of this regimen in these patients.
3. Determine the antileukemic/anti-MDS activity of this regimen in these patients.

Secondary

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

Entry 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/mm³ and/or platelet count < 20,000/mm³
    
    
    
    • Chronic myelomonocytic leukemia with > 5% blast cells in the bone marrow
    
    
    
    • Chronic myelomonocytic leukemia with neutrophil count > 16,000/mm³ OR monocyte count > 2,600/mm³
    
    
    
  
  
  
  • 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

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

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

Expected Enrollment

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

Outcomes

Rate of complete remission (CR) or complete remission with incomplete recovery of platelets (CRp) as measured by Cheson response criteria after the start of treatment
Severe toxicity after the start of treatment

Disease-free survival from CR/CRp
Duration of overall survival
Severity of pancytopenia and duration of recovery in patients who reached CR/CRp after the start of treatment

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.



• Group 2 (for patients with an HLA-matched sibling donor): 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.
  • Arm II: 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.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Theo De Witte, MD, PhD, Study coordinator		Ph: 31-24-361-4762 Email: l.brinkman@hemat.umcn.nl

Registry Information
Official Title		Idarubicin and Ara-C in Combination with Gemtuzumab-Ozogamicin (IAGO) for Young Untreated Patients, without an HLA Identical Sibling, with High Risk MDS or AML Developing After a Preceding Period with MDS During 6 Months Duration: A Phase II Study
Trial Start Date		2003-11-04
Registered in ClinicalTrials.gov		NCT00077116
Date Submitted to PDQ		2003-12-10
Information Last Verified		2006-11-19

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