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

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ClinicalTrials.gov Identifier: NCT03810196
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
Nancy Bunin, Children's Hospital of Philadelphia

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.

Condition or disease Intervention/treatment Phase
Acute Leukemia Acute Myeloid Leukemia Myelodysplastic Syndromes Acute Lymphoblastic Leukemia Mixed Lineage Leukemia Lymphoblastic Lymphoma Burkitt Lymphoma Juvenile Myelomonocytic Leukemia Device: CliniMACS Cell Processing System for TCRαβ + T Cell and CD45RA Depleted Peripheral Stem Cell Addback Not Applicable

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) if there is no GVHD present at Day 21. A short course of GVHD prophylaxis will be used after CD45RA depletion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 1, 2019
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2024


Arm Intervention/treatment
TBI regimen
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).
Device: CliniMACS Cell Processing System for TCRαβ + T Cell and CD45RA Depleted Peripheral Stem Cell Addback
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 who exhibit no GVHD at Day 21 will receive CD45RA depleted infusion.

TBI or busulfan regimen
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).
Device: CliniMACS Cell Processing System for TCRαβ + T Cell and CD45RA Depleted Peripheral Stem Cell Addback
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 who exhibit no GVHD at Day 21 will receive CD45RA depleted infusion.




Primary Outcome Measures :
  1. Incidence of acute graft vs. host disease (GVHD) [ Time Frame: Up to 100 days post-transplantation ]
    Incidence of acute graft vs. host disease (GVHD) (reaction of donor immune cells against host tissues)



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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: Patients <25 years.
  2. First allogeneic HSCT only.
  3. 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
  4. Evaluation of organ and infectious status as per our Bone Marrow Transplant standard operating procedure (BMT SOP).
  5. Signed consent by parent/guardian or able to give consent if >18 years.

Exclusion Criteria:

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

Donor selection and eligibility

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03810196


Contacts
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Contact: Barbara McGlynn, RN, BSN 215-590-1303 MCGLYNN@email.chop.edu

Locations
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United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Megan Atkinson       atkinsonm@email.chop.edu   
Contact: Barbara McGlynn       mcglynn@email.chop.edu   
Sponsors and Collaborators
Children's Hospital of Philadelphia
Investigators
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Principal Investigator: Nancy Bunin, MD Children's Hospital of Philadelphia

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Responsible Party: Nancy Bunin, Director, Blood & Marrow Transplant Section, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT03810196     History of Changes
Other Study ID Numbers: 18-015286
First Posted: January 18, 2019    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Additional relevant MeSH terms:
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Mycoses
Burkitt Lymphoma
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Lymphoid
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Myelodysplastic-Myeloproliferative Diseases
Busulfan
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors