TCR Alpha/Beta and CD19-deplete Haplo-HSCT

Phase 2

Withdrawn

• Conditions: Other Hematologic Condition; Pediatric Patients; Hematologic Malignancy
• Interventions: Device: CliniMACS Plus Instrument

• Registration Number: NCT05288595
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study First Submitted: 2022-03-10
• Study First Submitted QC: 2022-03-10
• Study First Posted: 2022-03-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-18
• Study Start: 2024-12
• Primary Completion: 2026-04
• Study Completion: 2028-04

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 50

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pediatric patients with malignant or non-malignant hematologic condition	CliniMACS Plus Instrument	The infusion of the final TCRαβ/CD19 depleted product will be given through the recipient's central venous catheter and will be administered fresh, without cryopreservation whenever possible. If the product must be cryopreserved and then thawed, this will be done according to institutional standards.

Primary Outcome Measures

Name	Time	Method
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.	5 years	Grade to be determined using Acute GVHD Staging Scale

Secondary Outcome Measures

Name	Time	Method
Number of patients with non-engraftment	100 days	Defined as the lack of donor-derived neutrophil engraftment
Post-HCT infections	100 days	Incidence of bacterial, fungal, and viral infections at day +100
Number of patients with relapse	1 year	Interval from transplant to relapse/recurrence of disease
Number of treatment-related mortality (TRM)	1 year	Defined as death due to regimen-related toxicity or GVD.
Disease-free Survival (DFS) measured in days	1 year	Defined as the minimum time interval from transplant to relapse/recurrence of disease, death or last follow-up.
Overall Survival (OS) measured in days	1 year	Determined at 1 year post-HCT
Immune Reconstitution	1 year	Incidence of absolute CD4+ T-cell count \>400 cells at 1 year post-HCT

Trial Locations

Locations (1)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States