Haploidentical HCT for Severe Aplastic Anemia

Summary

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?

Conditions

• Aplastic Anemia
• Bone Marrow Failure Syndrome

Interventions

DRUG

Anti-Thymocyte Globulin (Rabbit)

Given intravenously (IV)

DRUG

Fludarabine

Given intravenously (IV)

DRUG

Cyclophosphamide

Given intravenously (IV)

DRUG

Mesna

Given intravenously (IV)

DRUG

G-CSF

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

RADIATION

Total Lymphoid Irradiation (TLI)

TLI will be given at 800 cGy total dose in 4 fractions.

DEVICE

CliniMACS

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.

BIOLOGICAL

HPC, A Infusion

Given intravenously Day 0-HPC, A Infusion (TCR αβ+/CD19+-depleted graft)

BIOLOGICAL

CD45RA-depleted DLI

CD45RA-depleted DLI will be given at least ONE week after engraftment

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Amr Qudeimat, MD · St. Jude Children's Research Hospital

• Akshay Sharma, MBBS · St. Jude Children's Research Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-01-21

Primary Completion

2029-07-01

Completion

2030-07-01

FDA Device

Yes

Countries

• United States

Study Locations