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

Leukemia Clinical Trial

Official title:

Conditioning With Targeted Busulfan, Cyclophosphamide and Thymoglobulin for Allogeneic Marrow or Peripheral Blood Stem Cell (PBSC) Transplantation for Myelodysplasia and Myeloproliferative Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00054340
• Other study ID #: 1723.00
• Secondary ID: FHCRC-1723.00CDR
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 5, 2003
• Last updated: May 12, 2010
• Start date: October 2002
• Est. completion date: September 2006

Study information

• Verified date: May 2010
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

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

• No cardiac insufficiency requiring treatment

• No symptomatic coronary artery disease

Pulmonary

• 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

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

Study Design

Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Preleukemia
• Syndrome

Intervention

Biological:
• anti-thymocyte globulin

Drug:
• busulfan

• cyclophosphamide

• cyclosporine

• methotrexate

Procedure:
• allogeneic bone marrow transplantation

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,