NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia
Condition: Severe Aplastic Anemia; Aplastic Anemia; Bone Marrow Failure; Immunosuppression
MeSH terms: Anemia; Anemia, Aplastic; Bone Marrow Failure Disorders; Pancytopenia
Intervention: Thymoglobulin; Fludarabine; Cyclophosphamide; Total body irradiation; Tacrolimus; Mycophenolate mofetil
Intervention description: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily; Days -6 through -2: 30 mg/m^2 IV daily; Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily; Day -1: 200 centigray (cGy) in a single fraction; Start on Day 5 through Day 365; Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Fludarabine; Tacrolimus; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Healthy volunteers: No
Keywords: immunosuppression; nonmyeloablative; non-myeloablative; allogeneic; tacrolimus; bone marrow; bone marrow transplant; cyclophosphamide; thymoglobulin; ATG; fludarabine

Summary:

      Our primary objective is to determine if it is feasible for previously untreated severe
      aplastic anemia (SAA) patients to be transplanted using non-myeloablative conditioning and
      post transplantation cyclophosphamide.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of inherited or acquired severe aplastic anemia (SAA)

          -  One of the following available donors:

               1. HLA-haploidentical relative

               2. If recipient is >= 40 years old, may use HLA-matched related donor

               3. For recipients with inherited bone marrow failure syndromes (IBMFS) with clear
                  evidence of same disorder in potential related donors, may use 10/10 matched
                  unrelated donor

          -  Recipient and/or legal guardian must sign protocol informed consent

          -  Donor must be willing to donate bone marrow

          -  Left ventricular ejection fraction (LVEF) >= 40%. For recipients < 13 years old,
             shortening fraction >= 26% may be used instead.

          -  Bilirubin < 3 x upper limit of normal (ULN) for age, unless patient has Gilbert's
             disease

          -  aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x ULN for age

          -  For patients >= 13 years old: estimated creatinine clearance > 50 mL/min using
             Cockcroft-Gault formula and actual body weight

          -  For patients >= 1 but < 13 years old: glomerular filtration rate (GFR) estimated by
             updated Schwartz formula >= 90 mL/min/1.73 m^2. If estimated GFR is < 90 mL/min/1.73
             m^2, 24-hour measured creatinine clearance must be > 50 mL/min/1.73 m^2.

          -  For patients >= 8 years old, diffusing capacity of the lung for carbon monoxide (DLCO)
             (corrected for hemoglobin) > 40%; forced expiratory volume at one second (FEV1) > 50%;
             forced vital capacity (FVC) > 50%

          -  For patients < 8 years old or unable to undergo pulmonary function testing: no
             evidence of dyspnea at rest; no need for supplemental oxygen; oxygen saturation > 92%
             on room air

          -  Karnofsky/Lansky status (depending on age) >= 70%

          -  Females and males of childbearing potential must agree to practice 2 effective methods
             of contraception at the same time. If unwilling, they must agree to complete
             abstinence.

        Exclusion Criteria:

          -  Previous administration of immunosuppressive therapy for SAA.

          -  Fanconi anemia. At minimum, this diagnosis must be excluded by diepoxybutane (DEB) or
             equivalent testing on peripheral blood or marrow in patients < 30 years old.

          -  Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome
             (pre-MDS) or MDS on bone marrow examination

          -  Presence of anti-donor antibodies

          -  Prior allogeneic stem cell transplant

          -  Prior solid organ transplant

          -  Uncontrolled bacterial, viral, or fungal infection

          -  HIV seropositivity

          -  Active hepatitis B or C infection determined by serology and/or nucleic acid testing
             (NAT)

          -  Pregnancy or active breastfeeding

          -  Prior malignancies except: resected basal carcinoma or treated cervical carcinoma in
             situ; cancer treated with curative intent > 5 years previously. Other prior cancers
             will not be allowed unless approved by the PI.