Haploidentical HCT for Severe Aplastic Anemia
- Conditions
- Aplastic AnemiaBone Marrow Failure Syndrome
- Registration Number
- NCT04558736
- Lead Sponsor
- St. Jude Children's Research Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 21
Inclusion Criteria for Transplant Recipient<br><br> 1. Age less than or equal to 21 years at time of enrollment.<br><br> 2. Confirmed diagnosis of SAA or a single lineage cytopenia<br><br> (a) SAA or single lineage cytopenia will be defined as follows:<br><br> - i. Bone marrow cellularity < 25% or hypocellular marrow for age, AND<br><br> - ii. One or more of the following (in peripheral blood): (i) Neutrophils < 0.5<br> x10^9/L (ii) Platelets < 20 x10^9/L, or platelet transfusion dependence (iii)<br> Hemoglobin <8g/dL, or red blood cell transfusion dependence<br><br> 3. Does not have a suitable HLA-matched sibling donor (MSD) or volunteer 10/10<br> HLA-matched unrelated donor (MUD) available in the necessary time for progenitor<br> cell donation.<br><br> 4. Failed at least one trial of immunosuppressive therapy (IST) by being refractory<br> (persistence of severe cytopenias and fulfillment of SAA disease criteria at least 3<br> months after initial IST) or having relapsed (initial improvement of cytopenias<br> after first-line IST but then a later return to fulfillment of SAA disease criteria<br> when IST is decreased or ceased). IST could have included ATG based regimens,<br> calcineurin inhibitors and/or other higher dose therapy directed at the treatment of<br> primary SAA. Patients with very severe aplastic anemia who are likely not to benefit<br> from IST do not need to have failed a trial of IST and can proceed directly to HCT<br> if they meet the rest of the criteria.<br><br> 5. Has a suitable single haplotype matched (= 3 of 6) family member donor.<br><br> 6. Patient and/or legal guardian must sign informed consent for HCT.<br><br> 7. Adequate organ function defined as:<br><br> 1. Left ventricular ejection fraction > 40% or shortening fraction = 25%.<br><br> 2. Creatinine clearance (CrCl) or glomerular filtration rate (GFR) = 50 ml/<br> min/1.73m2.<br><br> 3. Forced vital capacity (FVC) = 50% of predicted value; or pulse oximetry<br><br> 4. = 92% on room air if patient is unable to perform pulmonary function testing.<br><br> 5. Karnofsky or Lansky (age-dependent) performance score = 50.<br><br> 6. Bilirubin = 3 times the upper limit of normal for age.<br><br> 7. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) = 5 times<br> the upper limit of normal for age.<br><br> 8. Females and males of childbearing potential must agree to practice 2 effective<br> methods of contraception at the same time or agree to abstinence until after the<br> last dose of chemotherapy has been administered<br><br>Exclusion Criteria for Transplant Recipient:<br><br> 1. Diagnosis of Fanconi anemia. Fanconi anemia must be excluded by diepoxybutane (DEB)<br> or equivalent testing.<br><br> 2. Known clinical or genetic diagnosis of dyskeratosis congenita<br><br> 3. Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-<br> MDS) or MDS on marrow examination (e.g. Monosomy 7).<br><br> 4. Diagnosis of myelodysplastic syndrome (MDS).<br><br> 5. Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined<br> as a positive cross-match test of any titer by complement- dependent cytotoxicity or<br> flow cytometric testing or the presence of anti- donor HLA antibody to the high<br> expression loci HLA-A, B, C, DRB1, or DPB1 with mean fluorescence intensity (MFI) ><br> 1000 by solid phase immunoassay).<br><br> 6. Prior allogeneic hematopoietic cell transplant.<br><br> 7. Prior solid organ transplant.<br><br> 8. Known life-threatening reaction (i.e., anaphylaxis) to ATG that would prohibit use<br> for the patient.<br><br> 9. Uncontrolled bacterial, viral, or fungal infection at the time of enrollment.<br> Uncontrolled is defined as progression or no clinical improvement on appropriate<br> medical treatment.<br><br> 10. Female patients who are pregnant (per institutional practice) or breast- feeding.<br><br> 11. Prior malignancies except resected basal cell carcinoma or treated cervical<br> carcinoma in situ. Cancer treated with curative intent > 5 years previously will be<br> allowed. Cancer treated with curative intent = 5 years previously will not be<br> allowed unless approved by the PI.<br><br> 12. Alemtuzumab or ATG within 2 weeks of enrollment.<br><br>Inclusion Criteria for Haploidentical Donor<br><br> 1. At least single haplotype matched (= 3 of 6) family member.<br><br> 2. At least 18 years of age.<br><br> 3. HIV negative.<br><br> 4. Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days<br> prior to enrollment (if female).<br><br> 5. Not breast feeding.<br><br> 6. Related donors must be ruled out for telomere disease by appropriate clinical and<br> diagnostic measures (for example, clinical evaluation, telomere length testing,<br> genetic testing, and/or bone marrow examination).<br><br> 7. The HAPLO donor and/or legal guardian must be able to sign informed consent<br> documents.<br><br> 8. The potential HAPLO donor must be willing and able to donate PBSCs.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Engraftment;Overall and event free survival
- Secondary Outcome Measures
Name Time Method Graft vs host disease;Graft rejection;Viral reactivation;Immune reconstitution