Haploidentical HCT for Severe Aplastic Anemia

Part of paid clinical trials in Memphis, Tennessee.

Sponsor
St. Jude Children's Research Hospital
Study ID
NCT04558736
Phase
PHASE2
Status
Recruiting
Apply to this trial

Conditions

Eligibility Criteria

Sex
ALL
Age
N/A - 21 Years
Healthy Volunteers
Not accepted

Interventions

  • Anti-Thymocyte Globulin (Rabbit) — DRUG
    Given intravenously (IV)
  • Fludarabine — DRUG
    Given intravenously (IV)
  • Cyclophosphamide — DRUG
    Given intravenously (IV)
  • Mesna — DRUG
    Given intravenously (IV)
  • G-CSF — DRUG
    Filgrastim is a human granulocyte colony-stimulating factor (G-CSF), produced by recombinant DNA technology. Dosage and Route of Administration: 5mcg/kg subcutaneous or intravenous daily until ANC \>2000 for 2 consecutive days, or as clinically indicated
  • Total Lymphoid Irradiation (TLI) — RADIATION
    TLI will be given at 800 cGy total dose in 4 fractions.
  • CliniMACS — DEVICE
    The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
  • HPC, A Infusion — BIOLOGICAL
    Given intravenously Day 0-HPC, A Infusion (TCR αβ+/CD19+-depleted graft)
  • CD45RA-depleted DLI — BIOLOGICAL
    CD45RA-depleted DLI will be given at least ONE week after engraftment

Study Details

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?

Key Dates

Start date
Jan 21, 2021
Status verified
Jul 2025
Primary completion
Jul 1, 2029
Completion
Jul 1, 2030

Study Design

Enrollment
21 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Haploidentical HCT
    To assess the safety and efficacy of haploidentical donor transplantation for patients with severe aplastic anemia who lack an available HLA-matched donor. The goal of this study is to develop a novel, reduced-toxicity, post-transplant pharmacologic immunosuppression (GVHD prophylaxis)- free, highly tolerogenic haploidentical transplant regimen that is associated with few post- transplant complications or late toxicities and is available promptly to all patients, irrespective of matched donor availability. Cells for infusion are prepared using the CliniMACS System.

Primary Outcome Measure

Engraftment [ Time Frame: 30 days ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
St. Jude Children's Research HospitalMemphisTennessee38105
Amr Qudeimat, MD
[email protected]
866-278-5833
Amr Qudeimat, MD (PRINCIPAL_INVESTIGATOR)
Akshay Sharma, MD (PRINCIPAL_INVESTIGATOR)

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