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

This study is no longer recruiting patients.

Sponsors and Collaborators: Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)

Purpose

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 Treatment or Intervention Phase
acute leukemia
chronic myeloproliferative disorders
Graft Versus Host Disease
myelodysplastic and myeloproliferative disease
 Drug: anti-thymocyte globulin
 Drug: busulfan
 Drug: cyclophosphamide
 Drug: cyclosporine
 Drug: methotrexate
 Procedure: allogeneic bone marrow transplantation
 Procedure: biological response modifier therapy
 Procedure: bone marrow ablation with stem cell support
 Procedure: bone marrow transplantation
 Procedure: chemotherapy
 Procedure: graft versus host disease prophylaxis/therapy
 Procedure: peripheral blood stem cell transplantation
 Procedure: supportive care/therapy
Phase I
Phase II

MedlinePlus related topics:  Blood and Blood Disorders;   Bone Marrow Diseases;   Cancer;   Cancer Alternative Therapy;   Immune System and Disorders;   Leukemia, Adult Acute;   Leukemia, Adult Chronic;   Leukemia, Childhood

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I/II Study of Conditioning With Busulfan, Cyclophosphamide, and Anti-Thymocyte Globulin to Reduce Graft-Versus-Host Disease in Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Further Study Details: 

OBJECTIVES:

  • 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.

  • 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.

Eligibility

Ages Eligible for Study:  up to  65 Years,  Genders Eligible for Study:  Both

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

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

Pulmonary

  • No severe or mild hypoxemia
  • pO
  • 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

Other

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

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

Location Information


Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109,  United States

Study chairs or principal investigators

H. Joachim Deeg, MD,  Study Chair,  Fred Hutchinson Cancer Research Center   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000270397; FHCRC-1723.00; NCT00054340
Record last reviewed:  March 2005
Last Updated:  March 22, 2005
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00054340
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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