Haploidentical HCT for Severe Aplastic Anemia

Launched by ST. JUDE CHILDREN'S RESEARCH HOSPITAL · Sep 15, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a new way to treat severe aplastic anemia (SAA), a serious condition where the bone marrow fails to produce enough blood cells. In this trial, patients will receive a type of stem cell transplant using blood-forming cells from a family member who is not a perfect match. The goal is to learn how well this method works, how it affects the patients' health, and how long they survive after the transplant. Key things researchers will look at include how quickly the transplanted cells start to grow in the patient's body and how well they do over the course of a year.

To be eligible for this trial, patients must be 21 years old or younger, have a confirmed diagnosis of SAA, and not have a fully matched donor available. They should also have tried at least one treatment for their condition that did not work. The trial is currently recruiting participants, and those who join can expect to undergo a series of tests and treatments, including chemotherapy and the transplant itself. This study aims to not only improve treatment for SAA but also to provide more insights into how the immune system reacts after the transplant. If you or someone you know is considering participation, it’s important to discuss the details and potential risks with a healthcare provider.

Gender

ALL

Eligibility criteria

• • Inclusion Criteria for Transplant Recipient
• • 1. Age less than or equal to 21 years at time of enrollment.
• • 2. Confirmed diagnosis of SAA or a single lineage cytopenia
• (a) SAA or single lineage cytopenia will be defined as follows:
• • i. Bone marrow cellularity \< 25% or hypocellular marrow for age, AND
• • ii. One or more of the following (in peripheral blood): (i) Neutrophils \< 0.5 x10\^9/L (ii) Platelets \< 20 x10\^9/L, or platelet transfusion dependence (iii) Hemoglobin \<8g/dL, or red blood cell transfusion dependence
• • 3. Does not have a suitable HLA-matched sibling donor (MSD) or volunteer 10/10 HLA-matched unrelated donor (MUD) available in the necessary time for progenitor cell donation.
• • 4. Failed at least one trial of immunosuppressive therapy (IST) by being refractory (persistence of severe cytopenias and fulfillment of SAA disease criteria at least 3 months after initial IST) or having relapsed (initial improvement of cytopenias after first-line IST but then a later return to fulfillment of SAA disease criteria when IST is decreased or ceased). IST could have included ATG based regimens, calcineurin inhibitors and/or other higher dose therapy directed at the treatment of primary SAA. Patients with very severe aplastic anemia who are likely not to benefit from IST do not need to have failed a trial of IST and can proceed directly to HCT if they meet the rest of the criteria.
• • 5. Has a suitable single haplotype matched (≥ 3 of 6) family member donor.
• • 6. Patient and/or legal guardian must sign informed consent for HCT.
• 7. Adequate organ function defined as:
• • 1. Left ventricular ejection fraction \> 40% or shortening fraction ≥ 25%.
• • 2. Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/ min/1.73m2.
• • 3. Forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry
• • 4. ≥ 92% on room air if patient is unable to perform pulmonary function testing.
• • 5. Karnofsky or Lansky (age-dependent) performance score ≥ 50.
• • 6. Bilirubin ≤ 3 times the upper limit of normal for age.
• • 7. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age.
• • 8. Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time or agree to abstinence until after the last dose of chemotherapy has been administered
• Exclusion Criteria for Transplant Recipient:
• • 1. Diagnosis of Fanconi anemia. Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing.
• • 2. Known clinical or genetic diagnosis of dyskeratosis congenita
• • 3. Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre- MDS) or MDS on marrow examination (e.g. Monosomy 7).
• • 4. Diagnosis of myelodysplastic syndrome (MDS).
• • 5. 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).
• • 6. Prior allogeneic hematopoietic cell transplant.
• • 7. Prior solid organ transplant.
• • 8. Known life-threatening reaction (i.e., anaphylaxis) to ATG that would prohibit use for the patient.
• • 9. Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as progression or no clinical improvement on appropriate medical treatment.
• • 10. Female patients who are pregnant (per institutional practice) or breast- feeding.
• • 11. 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 PI.
• • 12. Alemtuzumab or ATG within 2 weeks of enrollment.
• • Inclusion Criteria for Haploidentical Donor
• • 1. At least single haplotype matched (≥ 3 of 6) family member.
• • 2. At least 18 years of age.
• • 3. HIV negative.
• • 4. Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
• • 5. Not breast feeding.
• • 6. Related donors must be ruled out for telomere disease by appropriate clinical and diagnostic measures (for example, clinical evaluation, telomere length testing, genetic testing, and/or bone marrow examination).
• • 7. The HAPLO donor and/or legal guardian must be able to sign informed consent documents.
• • 8. The potential HAPLO donor must be willing and able to donate PBSCs.