TCR Alpha/Beta and CD19-deplete Haplo-HSCT

NCT05288595 | Withdrawn Phase 2 DMC FDA Device

• 1 other identifier: 20-2336.cc
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Pediatric Patients; Hematologic Malignancy; Other Hematologic Condition

Keywords

Donor; granulocyte stimulating factor (GCSF); apheresis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Number of patients with non-engraftment

  100 days

• Number of patients with relapse

  1 year

• Number of treatment-related mortality (TRM)

  1 year

• Disease-free Survival (DFS) measured in days

  1 year

• Overall Survival (OS) measured in days

  1 year

Study Arms (1)

Pediatric patients with malignant or non-malignant hematologic condition

EXPERIMENTAL

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

Interventions

CliniMACS Plus Instrument DEVICE

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.

Pediatric patients with malignant or non-malignant hematologic condition

Eligibility Criteria

• Age: 31 Days - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 31 days to \<30 years
• 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.
• Clinical remission for patients with acute leukemia (MDS/AML excluded) or lymphoma
• 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
• 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
• Able to give informed consent if ≥ 18 years, or with legal guardian capable of giving informed consent if \< 18 years
• Provision of signed and dated informed consent form

You may not qualify if:

• Uncontrolled, active infection at time of HCT
• HIV positivity
• Cardiac ejection fraction \<45%
• Creatinine clearance \<60 mL/min/1.72 mL
• 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
• Serum ALT \>5x upper limit of normal or bilirubin \>2
• Performance score (Lansky or Karnofsky) \<50
• Pregnant or lactating females, as many medications necessary for a successful HCT are potentially harmful to unborn babies and infants.

Sponsors & Collaborators

• University of Colorado, Denver: lead

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Alisa B Lee Sherick

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 10, 2022
• First Posted: March 21, 2022
• Study Start: December 1, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share