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CD45RA Depleted Peripheral Stem Cell Addback for Viral or Fungal Infections Post TCRαβ/CD19 Depleted HSCT

Primary Purpose

Acute Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndromes

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

CliniMACS Cell Processing System for TCRαβ + T Cell and CD45RA Depleted Peripheral Stem Cell Addback

About this trial

This is an interventional treatment trial for Acute Leukemia

Eligibility Criteria

undefined - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age: Patients <25 years.
First allogeneic HSCT only.
Disease eligibility: Acute leukemias at high risk for relapse including positive minimal residual disease at end consolidation, high risk cytogenetics, or relapse. Hematologic malignancies including: acute myeloid leukemia, myelodysplastic syndromes, acute lymphoblastic leukemia, mixed lineage or bi-phenotypic leukemia, lymphoblastic or Burkitts, juvenile myelomonocytic leukemia
Evaluation of organ and infectious status as per our Bone Marrow Transplant standard operating procedure (BMT SOP).
Signed consent by parent/guardian or able to give consent if >18 years.

Exclusion Criteria:

Patients who do not meet institutional disease, organ or infectious criteria
No suitable donor available for mobilized peripheral stem cells
Patients with genetic disorders including Fanconi anemia, Kostmann syndrome, dyskeratosis congenital or other DNA repair defects.
Patients with Hodgkin lymphoma or non-Burkitts, non-lymphoblastic lymphoma

Donor selection and eligibility

Unrelated donor meets National Marrow Donor Program criteria for donation
HLA testing/matching
Donor must be willing to undergo granulocyte colony stimulating factor (GCSF) mobilization and peripheral blood stem cell collection

Sites / Locations

Children's Hospital of PhiladelphiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

TBI regimen

TBI or busulfan regimen

Arm Description

Standard of care myeloablative regimens will be used based on disease type and clinical status at time of transplant. Patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma will receive total body irradiation (TBI) regimen (thiotepa, cyclophosphamide, TBI).

Standard of care myeloablative regimens will be used based on disease type and clinical status at time of transplant. Patients not diagnosed with ALL or lymphoblastic lymphoma may receive either total body irradiation (TBI) regimen (thiotepa, cyclophosphamide, TBI) or busulfan containing regimen (thiotepa, cyclophosphamide, busulfan).

Outcomes

Primary Outcome Measures

Incidence of acute graft vs. host disease (GVHD)

Incidence of acute graft vs. host disease (GVHD) (reaction of donor immune cells against host tissues)

Secondary Outcome Measures

Full Information

NCT ID

NCT03810196

First Posted

January 16, 2019

Last Updated

February 20, 2023

Sponsor

Children's Hospital of Philadelphia

1. Study Identification

Unique Protocol Identification Number

NCT03810196

Brief Title

CD45RA Depleted Peripheral Stem Cell Addback for Viral or Fungal Infections Post TCRαβ/CD19 Depleted HSCT

Official Title

CD45RA Depleted Peripheral Stem Cell Addback for Patients at Risk for Viral or Fungal Infections Post TCRαβ/CD19 Depleted Hematopoietic Stem Cell Transplant

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 1, 2019 (Actual)

Primary Completion Date

January 2024 (Anticipated)

Study Completion Date

January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Children's Hospital of Philadelphia

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The major morbidities of allogeneic hematopoietic stem cell transplant with non-human leukocyte antigen (HLA) matched siblings are graft vs host disease (GVHD) and life threatening infections. T depletion of the donor hematopoietic stem cell graft is effective in preventing GVHD, but immune reconstitution is slow, increasing the risk of infections. An addback of donor CD45RA (naive T cells) depleted cells may improve immune reconstitution and help decrease the risk of infections.

Detailed Description

The risk of severe graft versus host disease (GVHD) is increased with the use of unrelated and partially matched related donors. T cell depletion reduces the risk of severe GVHD, but immune reconstitution is delayed. Important memory T cells that may protect patients from fungal and viral infections are also removed in the T depletion process. CD45RA depletion has been studied both as a single step to reduce the risk of GVHD, and also, in conjunction with αβTCR depleted hematopoietic stem cell grafts to accelerate immune reconstitution. This is a single institutional pilot trial of this T cell depletion technique. Patients with acute leukemias at high risk for relapse are eligible to participate. Patients will be given CD45RA depleted donor peripheral stem cells (PSCs) following T depleted hematopoietic stem cell transplant (HSCT). A short course of GVHD prophylaxis will be used after CD45RA depletion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndromes, Acute Lymphoblastic Leukemia, Mixed Lineage Leukemia, Lymphoblastic Lymphoma, Burkitt Lymphoma, Juvenile Myelomonocytic Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

TBI regimen

Arm Type

Other

Arm Description

Arm Title

TBI or busulfan regimen

Arm Type

Other

Arm Description

Intervention Type

Device

Intervention Name(s)

CliniMACS Cell Processing System for TCRαβ + T Cell and CD45RA Depleted Peripheral Stem Cell Addback

Intervention Description

Peripheral stem cell (PSC) product will be processed using the CliniMACS device for TCRαβ and T cell depletion. Approximately 10% of the PSCs will undergo CD45RA depletion and cryopreservation. Patients will receive CD45RA depleted infusion after the TCRab PSCT.

Primary Outcome Measure Information:

Title

Incidence of acute graft vs. host disease (GVHD)

Description

Incidence of acute graft vs. host disease (GVHD) (reaction of donor immune cells against host tissues)

Time Frame

Up to 100 days post-transplantation

10. Eligibility

Sex

All

Maximum Age & Unit of Time

25 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age: Patients <25 years. First allogeneic HSCT only. Disease eligibility: Acute leukemias at high risk for relapse including positive minimal residual disease at end consolidation, high risk cytogenetics, or relapse. Hematologic malignancies including: acute myeloid leukemia, myelodysplastic syndromes, acute lymphoblastic leukemia, mixed lineage or bi-phenotypic leukemia, lymphoblastic or Burkitts, juvenile myelomonocytic leukemia Evaluation of organ and infectious status as per our Bone Marrow Transplant standard operating procedure (BMT SOP). Signed consent by parent/guardian or able to give consent if >18 years. Exclusion Criteria: Patients who do not meet institutional disease, organ or infectious criteria No suitable donor available for mobilized peripheral stem cells Patients with genetic disorders including Fanconi anemia, Kostmann syndrome, dyskeratosis congenital or other DNA repair defects. Patients with Hodgkin lymphoma or non-Burkitts, non-lymphoblastic lymphoma Donor selection and eligibility Unrelated donor meets National Marrow Donor Program criteria for donation HLA testing/matching Donor must be willing to undergo granulocyte colony stimulating factor (GCSF) mobilization and peripheral blood stem cell collection

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Barbara McGlynn, RN, BSN

Phone

215-590-1303

MCGLYNN@chop.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nancy Bunin, MD

Organizational Affiliation

Children's Hospital of Philadelphia

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Megan Atkinson

atkinsonm@chop.edu

First Name & Middle Initial & Last Name & Degree

Barbara McGlynn

mcglynn@chop.edu

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

CD45RA Depleted Peripheral Stem Cell Addback for Viral or Fungal Infections Post TCRαβ/CD19 Depleted HSCT

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