Text Size

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 has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00054340
First received: February 5, 2003
Last updated: May 12, 2010
Last verified: May 2010
History of Changes
  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 Intervention 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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Study Start Date: October 2002
Study Completion Date: September 2006
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.

  Eligibility

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00054340

Locations
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)
Investigators
Study Chair: H. Joachim Deeg, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier: NCT00054340     History of Changes
Other Study ID Numbers: 1723.00, FHCRC-1723.00, CDR0000270397
Study First Received: February 5, 2003
Last Updated: May 12, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

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:
Graft vs Host Disease
Leukemia
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antilymphocyte Serum
Busulfan
Cyclophosphamide
 Cyclosporins
Cyclosporine
Methotrexate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013