Ignite Creation Date:
2024-05-06 @ 3:12 PM
Last Modification Date:
2024-10-26 @ 1:45 PM
Study NCT ID:
NCT04558736
Status:
RECRUITING
Last Update Posted:
2023-08-21
First Post:
2020-09-09
Brief Title:
Haploidentical HCT for Severe Aplastic Anemia
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
Haploidentical Donor Hematopoietic Cell Transplantation for Patients With Severe Aplastic Anemia
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 patients 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 recipients innate and adaptive immune cells correlate with post-transplant immune repertoires and response profiles
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 recipients innate and adaptive immune cells correlate with post-transplant immune repertoires and response profiles
Detailed Description:
Immunosuppressant therapy IST is the main treatment for SAA for patients who do not have an HLA-matched sibling donor available for transplant But some patients with SAA do not respond to IST and some others relapse after IST HCT using an unrelated but HLA-matched donor is the only curative option for these patients but many patients lack a suitable HLA-matched donor St Jude is trying to increase donor options for these patients by using novel therapeutic strategies by combining two widely used of GVHD prophylaxis methods i selective T cell depletion and ii use of post-transplant cyclophosphamide This will allow expansion of the donor pool to include haploidentical donors as well as reduce the risk of GVHD The goal of this protocol is to test whether combining these GVHD prophylaxis approaches will allow use of haploidentical donors reduce risk of GVHD reduce transfusion dependence and improve immune reconstitution
For this study chemotherapy antibodies and radiation will be given to prepare the body to receive donor cells Participants will then be given the donor cell infusion
Patients will receive two types of donor blood cell products - a progenitor blood cell infusion and then a donor lymphocyte infusion Both the progenitor blood cell and the donor lymphocyte infusion will be processed in a laboratory at St Jude using a machine called the CliniMACS
In this clinical trial participants will receive a special type of progenitor blood cells called TCRαβ- depleted blood cells from the donor
After the donor progenitor cells have started to grow within the body engraftment participants will receive a second product that contains mature immune cells These immune cells called CD45RA-depleted lymphocytes or donor lymphocyte infusion DLI will help fight infections in the body after the transplant and strengthen the developing immune system
For this study chemotherapy antibodies and radiation will be given to prepare the body to receive donor cells Participants will then be given the donor cell infusion
Patients will receive two types of donor blood cell products - a progenitor blood cell infusion and then a donor lymphocyte infusion Both the progenitor blood cell and the donor lymphocyte infusion will be processed in a laboratory at St Jude using a machine called the CliniMACS
In this clinical trial participants will receive a special type of progenitor blood cells called TCRαβ- depleted blood cells from the donor
After the donor progenitor cells have started to grow within the body engraftment participants will receive a second product that contains mature immune cells These immune cells called CD45RA-depleted lymphocytes or donor lymphocyte infusion DLI will help fight infections in the body after the transplant and strengthen the developing immune system
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None