Haploidentical HCT for Severe Aplastic Anemia
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
AgeUp to 21
SponsorSt. Jude Children's Research Hospital
About this trial
This study is a prospective, single center phase II clinical trial in which patients with Severe Aplastic Anemia (SAA) ) will receive a haploidentical transplantation. The purpose of this study is to learn more about newer methods of transplanting blood forming cells donated by a family member that is not fully matched to the patient. This includes studying the effects of the chemotherapy, radiation, the transplanted cell product and additional white blood cell (lymphocyte) infusions on the patient's body, disease and overall survival. The primary objective is to assess the rate of engraftment at 30 days and overall survival (OS) and event free survival (EFS) at 1 year post-hematopoietic cell transplantation (HCT).
Primary Objectives
* To estimate the rate of engraftment at 30 days after TCR αβ+ T-cell-depleted graft infusion in patients receiving a single dose of post graft infusion cyclophosphamide. * To estimate the overall survival and event free survival at 1-year post transplantation.
Secondary Objectives
* To calculate the incidence of acute and chronic GVHD after HCT. * To calculate the rate of secondary graft rejection at 1-year post transplantation * To calculate the cumulative incidence of viral reactivation (CMV, EBV and adenovirus). * To describe the immune reconstitution after TCR αβ+ T-cell-depleted graft infusion at 1 month, 3 months, 6 months, 9 months, and 1 year.
Exploratory Objectives
* To longitudinally assess the phenotype and epigenetic profile of T-cells in SAA patients receiving HCT for SAA. * To assess the phenotype and epigenetic profile of T-cells in DLI administered to SAA patients post HCT. * To longitudinally assess CD8 T cell differentiation status in SAA patients using an epigenetic atlas of human CD8 T cell differentiation. * To examine the effector functions and proliferative capacity of CD8 T cells isolated from SAA patients before and after DLI. * Quantify donor derived Treg cells at different time points in patients received HCT. * Determine Treg activation status at different stages after HCT. * Are specific features of the DLI product associated with particular immune repertoire profiles post-transplant? * How does the diversity and functional profile of the DLI product alter the response to pathogens in the recipient? * Do baseline features of the recipient's innate and adaptive immune cells correlate with post-transplant immune repertoires and response profiles?
Eligibility criteria
Qualifiers
Age less than or equal to 21 years at time of enrollment.
Confirmed diagnosis of SAA or a single lineage cytopenia
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
Disqualifiers
Diagnosis of Fanconi anemia. Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing.
Known clinical or genetic diagnosis of dyskeratosis congenita
Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre- MDS) or MDS on marrow examination (e.g. Monosomy 7).
Diagnosis of myelodysplastic syndrome (MDS).
Trial design
Treatments tested in this trial
- Anti-Thymocyte Globulin (Rabbit)
- Fludarabine
- Cyclophosphamide
- Mesna
- G-CSF
- Total Lymphoid Irradiation (TLI)
- CliniMACS
- HPC, A Infusion
- CD45RA-depleted DLI
Treatment groups
21 Participants
are divided into 1 treatment groupSponsors and collaborators
Source ClinicalTrials.gov