Cyclophosphamide and Anti-thymocyte Globulin Followed By Methotrexate and Cyclosporine in Preventing Chronic Graft-Versus-Host Disease in Patients With Severe Aplastic Anemia Undergoing Donor Bone Marrow Transplant

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00343785
First received: June 22, 2006
Last updated: September 18, 2012
Last verified: September 2012
  Purpose

This clinical trial is studying how well giving cyclophosphamide together with anti-thymocyte globulin followed by methotrexate and cyclosporine works in preventing chronic graft-vs-host disease (GVHD) in patients with severe aplastic anemia undergoing donor bone marrow transplant. Giving low doses of chemotherapy, such as cyclophosphamide, before a donor bone marrow transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving anti-thymocyte globulin before and methotrexate and cyclosporine after transplant may stop this from happening


Condition Intervention Phase
Aplastic Anemia
Drug: cyclophosphamide
Biological: anti-thymocyte globulin
Drug: cyclosporine
Procedure: allogeneic bone marrow transplantation
Drug: methotrexate
Genetic: DNA analysis
Other: flow cytometry
Genetic: polymorphism analysis
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cyclophosphamide and Antithymocyte Globulin Conditioning Regimen for Marrow Transplantation From HLA-Matched Family Members for Severe Aplastic Anemia: Effect of Marrow Cell Dose on Chronic Graft-vs.-Host Disease: A Multi-Center Trial

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Incidence of chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Analyzed using cumulative incidence estimates, treating death or rejection as competing risk events. Confidence intervals will be calculated using the method described by Marubini and Valsecchi (1995). Risk factors for the development of chronic GVHD will be evaluated using Cox regression analyses methods.


Secondary Outcome Measures:
  • Engraftment [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From the time of enrollment until death from any cause, assessed up to approximately 6 years ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: February 2006
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (conditioning regimen, transplant, GVHD prophylaxis)
Patients receive a conditioning regimen comprising cyclophosphamide IV on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2. Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or PO twice daily on days -1 to 50, followed by a taper until 6 months after grafting.
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: anti-thymocyte globulin
Given IV
Other Names:
  • ATG
  • ATGAM
  • lymphocyte immune globulin
  • Thymoglobulin
Drug: cyclosporine
Given IV or PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Procedure: allogeneic bone marrow transplantation
Undergo allogeneic bone marrow transplantation
Other Names:
  • bone marrow therapy, allogeneic
  • bone marrow therapy, allogenic
  • transplantation, allogeneic bone marrow
  • transplantation, allogenic bone marrow
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Genetic: DNA analysis
Correlative studies
Other: flow cytometry
Correlative studies
Genetic: polymorphism analysis
Correlative studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Minimize the incidence of chronic GVHD by restricting the transplanted marrow dose to 2.0-2.5 x 10^8 nucleated cells/kg.

SECONDARY OBJECTIVES:

I. Engraftment and overall survival.

OUTLINE:

CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -5 to -2 and anti-thymocyte globulin IV over 4-10 hours on days -4 to -2.

TRANSPLANTATION: Patients undergo allogeneic bone marrow transplantation on day 0.

GVHD PROPHYLAXIS: Patients receive methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1 hour or orally (PO) twice daily on days -1 to 50, followed by a taper until 6 months after grafting.

After completion of study treatment, patients are followed up at on day 180, 1 year, 1.5 years, 2 years, 3 years, and yearly thereafter.

  Eligibility

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

Inclusion Criteria:

  • Any patient who has aplastic anemia with marrow failure involving 2 of the three following criteria: granulocytes < 500/uL; a corrected reticulocyte count of < 1%; platelet count of < 20,000/uL
  • Availability of an human leukocyte antigen (HLA)-matched family member
  • DONOR: Family member who is HLA-matched
  • DONOR: If more than one HLA-matched family member is available, priority will be given to a donor who is genotypically HLA-identical, of appropriate cytomegalovirus (CMV) serology, ABO compatible, and, in case of a female donor, non-parous

Exclusion Criteria:

  • Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure:

    • Patients who have developed clonal cytogenetic abnormalities or myelodysplastic syndrome (preleukemia)
    • Patients with Fanconi's anemia
    • Aplasia secondary to radiation or cytotoxic chemotherapy
    • Patients with paroxysmal nocturnal hemoglobinuria who have not developed aplastic anemia
  • Severe organ toxicities:

    • Cardiac insufficiency requiring treatment or symptomatic coronary artery disease;
    • Severe hypoxemia , partial pressure of oxygen (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted;
    • Impaired renal function (creatinine > 2 times upper limit of normal or estimated creatinine clearance < 60 ml/min)
  • Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
  • Human immunodeficiency virus (HIV)-positive patients
  • Females who are pregnant or breast-feeding
  • DONOR: Donors who have increase anesthetic risk and are not able psychologically and medically to tolerate the procedure
  • DONOR: HIV-positive donors
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00343785

Locations
United States, Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
United States, Wisconsin
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Investigators
Principal Investigator: Rainer Storb Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Storb, Rainer, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT00343785     History of Changes
Other Study ID Numbers: 2054.00, NCI-2010-01781, P01HL036444
Study First Received: June 22, 2006
Last Updated: September 18, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Graft vs Host Disease
Hematologic Diseases
Bone Marrow Diseases
Immune System Diseases
Antilymphocyte Serum
Cyclophosphamide
Cyclosporins
Cyclosporine
Methotrexate
Immunoglobulins
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on April 17, 2014