Clinical trial NCT03810196: 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
Overall status: RECRUITING
Phase: NA
Conditions: Acute Leukemia
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Acute Lymphoblastic Leukemia
Mixed Lineage Leukemia
Lymphoblastic Lymphoma
Burkitt Lymphoma
Juvenile Myelomonocytic Leukemia
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2019-01-18
Enrollment: 50
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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
5. Pregnant Participants

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

Primary outcomes:
measure: Incidence of acute graft vs. host disease (GVHD)
timeFrame: Up to 100 days post-transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Timothy Olson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: