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Combination Chemotherapy and Antithymocyte Globulin in Reducing Graft-Versus-Host Disease in Patients Undergoing Donor Stem Cell Transplantation For Myelodysplastic Syndrome or Myeloproliferative Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00054340
Recruitment Status : Completed
First Posted : February 6, 2003
Last Update Posted : May 14, 2010
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center

Brief Summary:

RATIONALE: Combining antithymocyte globulin with combination chemotherapy before donor peripheral stem cell transplantation may reduce the chance of developing graft-versus-host disease following transplantation.

PURPOSE: Phase I/II trial to study the effectiveness of combining antithymocyte globulin with busulfan and cyclophosphamide in reducing graft-versus-host disease in patients who are undergoing donor stem cell transplantation for myelodysplastic syndrome or other myeloproliferative disorder.

Condition or disease Intervention/treatment Phase
Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: methotrexate Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Phase 1 Phase 2

Detailed Description:


  • Determine the incidence of acute graft-vs-host disease (GVHD) requiring therapy in patients with myelodysplastic syndromes or myeloproliferative disorders treated with busulfan, cyclophosphamide, and anti-thymocyte globulin prior to transplantation with filgrastim (G-CSF)-mobilized peripheral blood stem cells (or bone marrow) from related or unrelated donors.
  • Determine the incidence of relapse and relapse-free survival in patients treated with this regimen.
  • Determine the incidence of non-relapse mortality by day 100 and 1 year posttransplantation in patients treated with this regimen.
  • Determine the incidence of Epstein-Barr virus reactivation, infections, and chronic GVHD in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of anti-thymocyte globulin.

  • Conditioning and graft-vs-host disease (GVHD) prophylaxis: Patients receive oral busulfan every 6 hours on days -7 to -4 (16 doses), cyclophosphamide IV on days -3 and -2, and anti-thymocyte globulin IV over 3 hours on days -3, -2, and -1.

Cohorts of 15 patients receive adjusted doses of anti-thymocyte globulin to determine the optimal dose at which Epstein-Barr virus (EBV) activation and GVHD are reduced. The optimal dose is the dose at which 2 consecutive cohorts receive the same regimen.

  • Stem cell transplantation: Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplantation on day 0.
  • Posttransplantation GVHD prophylaxis: Patients receive cyclosporine IV continuously on days -1 to 4 and then orally twice daily until day 180. Patients also receive methotrexate on days 1, 3, 6, and 11.

Patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 30-45 patients will be accrued for this study within 2 years.

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Study Type : Interventional  (Clinical Trial)
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Conditioning With Targeted Busulfan, Cyclophosphamide and Thymoglobulin for Allogeneic Marrow or Peripheral Blood Stem Cell (PBSC) Transplantation for Myelodysplasia and Myeloproliferative Disorders
Study Start Date : October 2002
Actual Study Completion Date : September 2006

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of 1 of the following:

    • Myelodysplastic syndromes (including those that have evolved to acute myeloid leukemia)
    • Myeloproliferative disorders

      • No chronic myelogenous leukemia
    • Other diseases eligible for conditioning with targeted busulfan, cyclophosphamide, and anti-thymocyte globulin that are not candidates for other studies
  • Available related or unrelated donor compatible for HLA-A, -B, -C, DRB1, and DQB1

    • A single allele mismatch at HLA-A, -B, -C, or DRB1 is allowed



  • 65 and under

Performance status

  • Not specified

Life expectancy

  • No severe limitation due to other diseases


  • Not specified


  • AST no greater than 2 times normal
  • No hepatic disease


  • Creatinine no greater than 2 times upper limit of normal OR
  • Creatinine clearance at least 50% for age, gender, and weight


  • No cardiac insufficiency requiring treatment
  • No symptomatic coronary artery disease


  • No severe or mild hypoxemia

    • pO_2 at least 70 mm Hg and DLCO at least 70% of predicted OR
    • pO_2 at least 80 mm Hg and DLCO at least 60% of predicted


  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • HIV negative


Biologic therapy

  • No growth factors given posttransplantation concurrently with methotrexate immunosuppression


  • Not specified

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00054340

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United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
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Study Chair: H. Joachim Deeg, MD Fred Hutchinson Cancer Research Center

Layout table for additonal information Identifier: NCT00054340     History of Changes
Other Study ID Numbers: 1723.00
CDR0000270397 ( Registry Identifier: PDQ )
First Posted: February 6, 2003    Key Record Dates
Last Update Posted: May 14, 2010
Last Verified: May 2010
Keywords provided by Fred Hutchinson Cancer Research Center:
graft versus host disease
polycythemia vera
chronic idiopathic myelofibrosis
essential thrombocythemia
untreated adult acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
chronic eosinophilic leukemia
chronic neutrophilic leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
childhood myelodysplastic syndromes
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Graft vs Host Disease
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Immune System Diseases
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists