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

July 13, 2012 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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

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. Giving healthy stem cells from a donor whose blood closely resembles the patient's blood will help the patient's bone marrow make new stem cells that become red blood cells, white blood cells, and platelets.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

  • 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.

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

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brugge, Belgium, 8000
        • AZ Sint-Jan
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-Luc
      • Brussels, Belgium, 1000
        • Institut Jules Bordet
      • Roeselare, Belgium, 8800
        • H. Hartziekenhuis - Roeselaere.
  • Germany
      • Heidelberg, Germany, D-69117
        • Ruprecht - Karls - Universitaet Heidelberg
  • Netherlands
      • Amsterdam, Netherlands, 1091 HA
        • Onze Lieve Vrouwe Gasthuis
      • Leiden, Netherlands, 2300 CA
        • Leiden University Medical Center
      • Nijmegen, Netherlands, NL-6500 HB
        • Universitair Medisch Centrum St. Radboud - Nijmegen
  • Switzerland
      • Basel, Switzerland, CH-4031
        • Universitaetsspital-Basel

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Theo De Witte, MD, PhD, Universitair Medisch Centrum St. Radboud - Nijmegen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2003

Primary Completion (Actual)

November 1, 2006

Study Registration Dates

First Submitted

February 10, 2004

First Submitted That Met QC Criteria

February 10, 2004

First Posted (Estimate)

February 11, 2004

Study Record Updates

Last Update Posted (Estimate)

July 16, 2012

Last Update Submitted That Met QC Criteria

July 13, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-06013

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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