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

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Supportive care, Treatment Closed 65 and under NCI FHCRC-1723.00 NCT00054340

Objectives

1. 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.
2. Determine the incidence of relapse and relapse-free survival in patients treated with this regimen.
3. Determine the incidence of non-relapse mortality by day 100 and 1 year posttransplantation in patients treated with this regimen.
4. Determine the incidence of Epstein-Barr virus reactivation, infections, and chronic GVHD in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• No growth factors given posttransplantation concurrently with methotrexate immunosuppression

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age

• 65 and under

Performance status

• Not specified

Life expectancy

• No severe limitation due to other diseases

Hematopoietic

• Not specified

Hepatic

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

Renal

• Creatinine no greater than 2 times upper limit of normal

  OR

• Creatinine clearance at least 50% for age, gender, and weight

Cardiovascular

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

Pulmonary

• No severe or mild hypoxemia
  • pO₂ at least 70 mm Hg and DLCO at least 70% of predicted

    OR

  • pO₂ at least 80 mm Hg and DLCO at least 60% of predicted

Other

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

H. Joachim Deeg, MD, Protocol chair		Ph: 206-667-5985 Email: jdeeg@fhcrc.org

Registry Information
Official Title		Conditioning with Targeted Busulfan, Cyclophosphamide and Thymoglobulin for Allogeneic Marrow or Peripheral Blood Stem Cell (PBSC) Transplantation for Myelodysplasia and Myeloproliferative Disorders
Trial Start Date		2002-10-07
Registered in ClinicalTrials.gov		NCT00054340
Date Submitted to PDQ		2002-12-31
Information Last Verified		2005-03-15
NCI Grant/Contract Number		P01-CA18029, HL36444, P30-CA15704

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