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

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00054340

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

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

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.

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.

Study Design

Study Type:

Interventional

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 :

Oct 1, 2002

Actual Study Completion Date :

Sep 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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