TCRαβ/CD19 Depletion of Stem Cell Grafts for Transplant

Acute Myeloid Leukemia Clinical Trial

Official title: A Feasibility Study Using the CliniMACS Device for T-Cell Receptor (TCR) αβ+/CD19+ Depleted Hematopoietic Stem Cells for Patients Undergoing Transplant

Status Not yet recruiting

Clinical Trial Summary

The CliniMACS® device is FDA-approved only for one indication (CD34+ selection). Additional use of this device outside of this indication requires the use of feasibility studies.

Children, adolescents and young adults with malignant and non-malignant conditions undergoing hematopoietic stem cell transplants will have stem cells selected using alpha-beta+/CD19+ cell depletion. This is a single arm feasibility study using this processing of peripheral stem cells with alternative donor sources (haploidentical, mismatched, matched unrelated) to determine efficacy as seen by engraftment and graft-versus-host disease (GVHD).

Clinical Trial Description

Hematopoietic stem cell transplantation (HSCT) is recognized as an effective cure for a wide range of diagnoses including hematologic malignancies, bone marrow failure syndromes, red blood cell disorders (sickle cell, beta thalassemia), white blood cell disorders (CGD), and immune deficiency disorders. Current therapy with allogeneic HCT from HLA-matched sibling donors has shown to be a potentially curative option for children with high-risk and/or relapsed hematologic malignancies (ALL/AML) as well as primary immune deficiency disorders (PID), however only 25-30% of patients have an HLA-identical matched sibling. Alternative stem cell sources include matched unrelated donors (MUD) and unrelated cord blood (UCB), however, the likelihood of finding an unrelated match can range between 29-79% depending on the patient's ethnic background. Since 2015, the CHLA Transplant and Cellular Therapy Program has performed approximately 90 ex vivo processed haploidentical transplants. Greater than 80% of our patients belong to racial/ethnic groups with limited unrelated donor availability, relying heavily on haploidentical donors. This lack of matched stem cells represents a significant access disparity for underrepresented minorities with life-threatening hematologic or immunologic conditions to undergo a potentially curative HSCT.

The FDA approved the use of the CliniMACS CD34+ Reagent System as a Humanitarian Use Device for the prevention of GVHD in patients with acute myeloid leukemia (AML) in first complete remission undergoing allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related donor. The CliniMACS CD34+ Reagent System decreases the risk of developing GVHD by efficiently removing donor T-cells from the graft prior to infusion by enriching CD34+ blood stem cells, which help to repopulate the patient's immune system. FDA approval was based on data from a phase II, single-arm, multi-center study conducted by the Blood and Marrow Transplant Clinical Trials Network that showed after an intensive myeloablative conditioning, receiving a stem cell transplant from a matched related donor processed through the CliniMACS CD34+ Reagent System as a GVHD prophylaxis led to a low incidence of chronic GVHD, about 19% at 2 years post-transplant. However, removal of all cells except CD34+ selected complicates immune recovery (delay in CD4+ cells) leading to higher rates of opportunistic viral infections and transplant-related mortality.

The use of CD34+ selected processing has facilitated approximately 42 HSCTs in combination of TCRαβ+/CD19 depletion at CHLA. The new approach to ex vivo processing utilizes negative depletion of cells thought to be responsible for the development of aGVHD, αβ TCR positive T-cells and includes simultaneous depletion of CD19+ B-cells. Since 2015, CHLA has conducted TCRαβ/CD19+ depleted HSCTs successfully on several protocols, including the ONC1401 KIR Study (IDE#16412). ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Graft Vs Host Disease
• Graft-versus-host-disease
• Hematologic Malignancy
• Hematologic Neoplasms
• Leukemia
• Neoplasms
• Non-hematologic Malignancy
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT05968170
• Study type: Interventional
• Source: Children's Hospital Los Angeles
• Contact: Elizabeth Kissell, MS
• Phone: 323-361-5286
• Email: ekissell@chla.usc.edu
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 1, 2023
• Completion date: July 1, 2035