TCR Alpha/Beta and CD19-deplete Haplo-HSCT

TCR Alpha/Beta and CD19-depleted Allogeneic Hematopoietic Cell Transplant for Malignant and Non-Malignant Disease

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.

Study Overview

• Status: Withdrawn
• Conditions: Hematologic Malignancy; Pediatric Patients; Other Hematologic Condition
• Intervention / Treatment: Device: CliniMACS Plus Instrument

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 30 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pediatric patients with malignant or non-malignant hematologic condition; 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.

Device: CliniMACS Plus Instrument; Miltenyi Biotec's CliniMACS Plus Instrument is to be used to TCRαβ CD19 deplete products utilized in this protocol. The CliniMACS Plus is an automated cell separation platform which is functionally closed, maintaining a sterile system for cell depletion and enrichment utilizing a magnetic separation column. Reagents and supplies are to be used for research only but are manufactured and tested under a quality system certified to ISO 13485. Should CD34 selection be required to augment stem cell dose, Miltenyi Biotec's CliniMACS® Plus CD34 Reagent System is FDA approved as a Humanitarian Use Device (HUD). The approved indication was the treatment of patients with acute myeloid leukemia (AML) undergoing myeloablative transplant from matched related allogeneic donors. The CliniMACS® Plus reagent system was approved to obtain an enriched CD34+ cell population for hematopoietic reconstitution without the need for GVHD prophylaxis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Grade to be determined using Acute GVHD Staging Scale	5 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Alisa B Lee Sherick, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 10, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 21, 2022

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: apheresis; Donor; granulocyte stimulating factor (GCSF)
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: 20-2336.cc

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes