NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia

• Status: Completed
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Treatments: Antilymphocyte Serum; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Mycophenolate mofetil; Mycophenolic Acid; Tacrolimus; Thymoglobulin

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.