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
Condition: Aplastic Anemia
MeSH terms: Anemia; Anemia, Aplastic
Intervention: cyclophosphamide; anti-thymocyte globulin; cyclosporine; allogeneic bone marrow transplantation; methotrexate; DNA analysis; flow cytometry; polymorphism analysis; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV or PO; Undergo allogeneic bone marrow transplantation; Given IV; Correlative studies; Correlative studies; Correlative studies; Correlative studies
Intervention MeSH terms: Cyclosporine; Cyclophosphamide; Methotrexate; Cyclosporins; Thymoglobulin; Antilymphocyte Serum; Immunoglobulins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility 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