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

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00054340

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 I Phase II

Study Type:	Interventional
Study Design:	Supportive Care, Open Label
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:

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Cyclophosphamide Busulfan Methotrexate Cyclosporine Cyclosporin

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
Primary Completion Date:	September 2006 (Final data collection date for primary outcome measure)

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

Study ID Numbers:	CDR0000270397, FHCRC-1723.00
Study First Received:	February 5, 2003
Last Updated:	July 2, 2009
ClinicalTrials.gov Identifier:	NCT00054340 History of Changes
Health Authority:	United States: Federal Government

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:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Cyclophosphamide
Cyclosporins
Leukemia
Preleukemia
Pathologic Processes

Antifungal Agents
Therapeutic Uses
Syndrome
Abortifacient Agents
Methotrexate
Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Disease
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 09, 2009