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 - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborators:	National Cancer Institute (NCI) National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00343785

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 II

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:

MedlinePlus related topics: Anemia Aplastic Anemia Bone Marrow Transplantation Cancer

Drug Information available for: Cyclophosphamide Methotrexate Cyclosporine Cyclosporin Immunoglobulins Globulin, Immune

U.S. FDA Resources

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.

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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	150
Study Start Date:	February 2006
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Marrow transplantation from HLA-matched family members 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

Arms

Assigned Interventions

Experimental: Marrow transplantation from HLA-matched family members

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, California
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609-1809
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Utah
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

National Cancer Institute (NCI)

National Heart, Lung, and Blood Institute (NHLBI)

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:	May 6, 2011
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
Cyclosporine
Cyclosporins
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
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Enzyme Inhibitors
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on February 09, 2012