A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Haploidentical Related, Partially HLA-Mismatched, or Matched Unrelated Bone Marrow for Newly Diagnosed Patients With Severe Aplastic Anemia
BMT CTN 2207 will investigate the use of marrow transplantation for treatment of severe aplastic anemia that has not previously been treated.
• Age 3 years to 75 years
• Confirmed diagnosis of acquired SAA defined as:
• a. Bone marrow cellularity \< 25% or variable marrow cellularity but with \< 30% residual hematopoietic cells deemed HYPOcellular for age AND b. Two (2) out of 3 of the following (in peripheral blood). i. Neutrophils \< 0.5 x109/L ii. Platelets \< 20 x109/L iii. Reticulocyte count \< 20 x109/L (\< 60 x 109/L using an automated analysis)
• No suitable fully matched related donor as per Investigator's discretion (6/6 match for HLA A and B at intermediate or high-resolution and DRB1 at high-resolution using deoxyribonucleic acid \[DNA\]-based typing) available.
• Available donor as defined in the protocol.
• Participant and/or legal guardian must sign informed consent.
• Adequate organ function defined by institutional transplant standards or defined as below:
‣ Cardiac: Left ventricular ejection fraction (LVEF) at rest \> 40% with no clinical signs of cardiac failure. For participants aged \< 13 years, shortening fraction (SF) ≥ 26% by echocardiogram or multigated acquisition (MUGA) may be substituted for LVEF.
⁃ Hepatic: Total bilirubin \< 2.0 mg/dL unless Gilbert's disease is present
⁃ Renal: For participants \> 13.0 years of age at the time of enrollment: estimated creatinine clearance (CrCl) \> 60 mL/minute (per institutional standard). For participants \< 13.0 years of age at enrollment: glomerular filtration rate (GFR) estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated GFR is \< 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be \> 50 mL/min/1.73 m2.
⁃ Pulmonary:
• i. For participants \> 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO, corrected/adjusted for hemoglobin \[Hb\]) \> 50%, or Spirometry with forced expiratory volume 1 (FEV1) \> 50% predicted (without administration of bronchodilator) and forced vital capacity (FVC) \> 50% predicted.
• ii. For participants \< 13.0 years of age unable to perform pulmonary function tests (PFTs) due to age or developmental ability: (1) no evidence of dyspnea at rest and (2) no need for supplemental oxygen and (3) O2 saturation \> 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care \[e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below 90%\]).
• Karnofsky or Lansky performance status ≥ 60%.
• Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence.