TCR Alpha/Beta and CD19-deplete Haplo-HSCT

Hematologic Malignancy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05288595
• Other study ID #: 20-2336.cc
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 2024
• Est. completion date: April 2028

Study information

• Verified date: February 2024
• Source: University of Colorado, Denver
• Contact: Kayla Pacheco
• Phone: 17207774151
• Email: kayla.pacheco[@]childrenscolorado.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: April 2028
• Est. primary completion date: April 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 31 Days to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Malignancy
• Hematologic Neoplasms
• Pediatric Patients

Intervention

Device:
• CliniMACS Plus Instrument
Miltenyi Biotec's CliniMACS Plus Instrument is to be used to TCRaß 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.

Locations

Country	Name	City	State
United States	Children's Hospital Colorado	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of severe (grade III-IV) acute graft-versus-host disease (GVHD) at day 100 after infusion of a TCRaß+/CD19+ negative, peripheral blood stem cell (PBSC) product without additional GVHD prophylaxis.	Grade to be determined using Acute GVHD Staging Scale	5 years
Secondary	Number of patients with non-engraftment	Defined as the lack of donor-derived neutrophil engraftment	100 days
Secondary	Number of patients with relapse	Interval from transplant to relapse/recurrence of disease	1 year
Secondary	Number of treatment-related mortality (TRM)	Defined as death due to regimen-related toxicity or GVD.	1 year
Secondary	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
Secondary	Overall Survival (OS) measured in days	Determined at 1 year post-HCT	1 year
Secondary	Immune Reconstitution	Incidence of absolute CD4+ T-cell count >400 cells at 1 year post-HCT	1 year
Secondary	Post-HCT infections	Incidence of bacterial, fungal, and viral infections at day +100	100 days