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Purpose:
Assess overall survival (OS) at 1 year post-hematopoietic stem cell transplantation (HSCT) from a haploidentical marrow donor in patients with severe aplastic anemia (SAA).
Status:
Recruiting
Bone Marrow Disease(s):
Associated Drug(s):
Phase:
Phase 2
Gender:
Female
Male
Age Group:
up to 76 years
Accepts Healthy Volunteers:
No
Details on clinicaltrials.gov:
Inclusion Criteria:
- Confirmed diagnosis of SAA defined as: Bone marrow cellularity < 25% or marrow cellularity < 50% but with < 30% residual hematopoietic cells; AND two out of three of the following (in peripheral blood): Neutrophils < 0.5 x109/L, Platelets < 20 x109/L, Reticulocyte count < 20 x109/L (< 60 x 109/L using an automated analysis)
- No suitable fully matched related (6/6 match for HLA-A and B at intermediate or high resolution and DRB1 at high resolution using DNA-based typing) or unrelated donor (8/8 match for HLA-A, B, C, and DRB1 at high resolution using DNA-based typing) available.
- Failed at least one trial of immunosuppressive therapy (IST) by being refractory or having relapsed.
- Available relative of the patient who is a haploidentical match, including biological parents, siblings or half siblings, children, uncles/aunts, first cousins, etc.
- Patient and/or legal guardian must sign informed consent for HSCT.
- The haplo donor and/or legal guardian must be able to sign informed consent documents.
- The potential haplo donor must be willing and able to donate bone marrow.
- The weight of the haplo donor must be ≥ 20 kg.
- Adequate organ function defined as:
- Cardiac: Left ventricular ejection fraction (LVEF) at rest ≥ 40%. For patients aged < 13 years, shortening fraction (SF) ≥ 26% by echocardiogram or MUGA may be substituted for LVEF.
- Hepatic: Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert’s Disease are allowed to exceed this limit) and AST and ALT < 5.0 x ULN for age.
- Renal:
- For patients > 13.0 years of age at the time of enrollment: estimated creatinine clearance > 50 mL/minute (using the Cockcroft-Gault formula and actual body weight). Please refer to Body Weight calculations in Appendix E.
- For patients < 13.0 years of age at enrollment: 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:
- For patients > 13.0 years of age: DLCO (corrected/adjusted for hemoglobin) > 40% and FEV1 > 50% predicted (without administration of bronchodilator) and FVC > 50% predicted.
- For patients < 13.0 years of age unable to perform 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.
Exclusion Criteria:
- Inherited bone marrow failure syndromes. At minimum, the diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing.
- Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. Monosomy 7).
- Diagnosis of myelodysplastic syndrome (MDS).
- Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence of anti-donor HLA antibody to the high expression loci HLA-A, B, C, DRB1, or DPB1 with mean fluorescence intensity (MFI) > 1000 by solid phase immunoassay).
- Prior allogeneic stem cell transplant.
- Prior solid organ transplant.
- Known life-threatening reaction (i.e., anaphylaxis) to Thymoglobulin® that would prohibit use for the patient as this study requires use of the Thymoglobulin® preparation of ATG.
- Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment.
- Seropositive for the human immunodeficiency virus (HIV).
- Active Hepatitis B or C determined by a detectable viral load of HBV or HCV.
- Female patients who are pregnant (per institutional practice) or breast-feeding.
- Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent > 5 years previously will be allowed. Cancer treated with curative intent ≤ 5 years previously will not be allowed unless approved by the Protocol Chairs and/or Protocol Officer.
- Alemtuzumab or ATG within 2 weeks of enrollment.