Clinical trial NCT05288595: TCR Alpha/Beta and CD19-deplete Haplo-HSCT
Official title: TCR Alpha/Beta and CD19-depleted Allogeneic Hematopoietic Cell Transplant for Malignant and Non-Malignant Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Pediatric Patients
Hematologic Malignancy
Other Hematologic Condition
Keywords: Donor
granulocyte stimulating factor (GCSF)
apheresis
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2022-03-21
Enrollment: 0
Sex: ALL
Minimum age (years): 31
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Eligible Patients with a hematologic disease who could benefit from HCT with an eligible mismatched related or unrelated donor per donor selection criteria. Patient/recipient admitted of HCT/start of preparative regimen and stem cell infusion
Primary purpose: TREATMENT

Brief summary: This is an open label, interventional, non-randomized, phase II trial of TCR alpha/beta and CD19-depeleted allogeneic HCT in pediatric patients with hematologic disease.

Detailed description: This is a single-site, open label, interventional, non-randomized, phase II trial of TCRαβ/CD19 deplete allogeneic HCT as donor source and sole GVHD prophylaxis in pediatric patients with either malignant or non-malignant hematologic disease who are eligable for allogeneic HCT, but lack a HLA-matched sibling donor.

Eligibility criteria: Inclusion Criteria:

1. Age 31 days to \<30 years
2. Have a malignant or non-malignant hematologic disease, defined as disease resulting from abnormal function of a cell of the hematopoietic stem cell lineage, that could benefit from an allogeneic HCT. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias/marrow failure, white blood cell abnormalities, red blood cell abnormalities, and platelet abnormalities.
3. Clinical remission for patients with acute leukemia (MDS/AML excluded) or lymphoma
4. Lack a healthy and willing HLA-identical related donor, with the exception of patients with FA who will be eligible with a willing HLA-identical related donor given the standard use of T-cell depletion in matched sibling donor HCT in FA
5. Have a related or an unrelated donor who meets the donor selection criteria, is healthy, willing, and able to receive GCSF with or without Plerixafor, and undergo apheresis through placement of catheters in the antecubital veins or a temporary central venous catheter
6. Able to give informed consent if ≥ 18 years, or with legal guardian capable of giving informed consent if \< 18 years
7. Provision of signed and dated informed consent form

Exclusion Criteria:

1. Uncontrolled, active infection at time of HCT
2. HIV positivity
3. Cardiac ejection fraction \<45%
4. Creatinine clearance \<60 mL/min/1.72 mL
5. Pulmonary diffusion capacity (adjusted for hemoglobin), FEV1, or FVC \<60% of predicted or an O2 saturation \<94% on room air if unable to perform pulmonary function testing
6. Serum ALT \>5x upper limit of normal or bilirubin \>2
7. Performance score (Lansky or Karnofsky) \<50
8. Pregnant or lactating females, as many medications necessary for a successful HCT are potentially harmful to unborn babies and infants.

Primary outcomes:
measure: Incidence of severe (grade III-IV) acute graft-versus-host disease (GVHD) at day 100 after infusion of a TCRαβ+/CD19+ negative, peripheral blood stem cell (PBSC) product without additional GVHD prophylaxis.
timeFrame: 5 years
Secondary outcomes:
measure: Number of patients with non-engraftment
timeFrame: 100 days
measure: Number of patients with relapse
timeFrame: 1 year
measure: Number of treatment-related mortality (TRM)
timeFrame: 1 year
measure: Disease-free Survival (DFS) measured in days
timeFrame: 1 year
measure: Overall Survival (OS) measured in days
timeFrame: 1 year
measure: Immune Reconstitution
timeFrame: 1 year
measure: Post-HCT infections
timeFrame: 100 days
Other outcomes:
Locations:
Study officials:
affiliation: University of Colorado, Denver
name: Alisa B Lee Sherick
role: PRINCIPAL_INVESTIGATOR
References: