Haploidentical Hematopoietic Cell Transplantation Using TCR Alpha/Beta and CD19 Depletion — HAPLOTAB  

Myelodysplastic Syndromes Clinical Trial

Official title: T-Cell Receptor Alpha Beta+/CD19+ Depletion in Haploidentical Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) for Adult and Pediatric Patients With Hematological Malignancies and Non-malignant Disorders

Status Recruiting

Clinical Trial Summary

Patients with medical conditions requiring allogeneic hematopoietic cell transplantation (allo-HCT) are at risk of developing a condition called graft versus host disease (GvHD) which carries a high morbidity and mortality. This is a phase I/II study that will test the safety and efficacy of hematopoietic cell transplantation (HCT) with ex-vivo T cell receptor Alpha/Beta+ and CD19 depletion to treat patients' underlying condition. This process is expected to substantially decrease the risk of GvHD thus allowing for the elimination of immunosuppressive therapy post-transplant. The study will use blood stem/progenitor cells collected from the peripheral blood of parent or other half-matched (haploidentical) family member donor. The procedure will be performed using CliniMACS® TCRα/β-Biotin System which is considered investigational.

Clinical Trial Description

This is a phase I/II study of haploidentical HCT (HHCT) with ex vivo TCRαβ+ and CD19+ depletion using the CliniMACS device in patients with hematological malignancies and non-malignant disorders. HHCT will be performed according to current standards of care at the Center for Cell and Gene Therapy (CAGT) within Texas Children's Hospital (TCH) and Houston Methodist Hospital (HMH), including the use of a standard chemotherapy conditioning regimens, supportive care and standard follow-up laboratory assessments. The study will determine efficacy of this strategy in terms of engraftment, and safety in terms of rates of acute and chronic graft versus Host Disease (GvHD), one-year overall survival (OS) and transplant-related mortality (TRM).

The peripheral blood hematopoietic cell product will undergo negative selection of TCR αβ following the standardized protocol in the user's manual for the CliniMACS (Miltenyi Biotech, Germany). TCR αβ+ T-cells are labeled by CliniMACS TCR αβ-Biotin (murine anti-TCR αβ monoclonal antibodies conjugated to biotin) which allows the TCR αβ+ T-cells to be magnetically labeled with CliniMACS Anti-Biotin Microbeads (murine anti-biotin monoclonal antibodies conjugated to superparamagnetic iron dextran particles) for depletion. The CD19+ B cells are labeled by CliniMACS CD19 microbeads which allows the CD19+ B cells to be magnetically labeled for depletion. All unlabeled cells are selected as target cells which should contain a minimum amount of TCR αβ+ and CD19+ cells. The microbeads used for labeling are approximately 50 nanometers in diameter and do not require removal prior to patient infusion.

In January 2014, the U.S. Food and Drug Administration (FDA) has approved the Miltenyi Biotec's 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 allo-HCT from HLA-matched related donor. ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia in Remission
• Acute Myeloid Leukemia in Remission
• Anemia
• Anemia, Aplastic
• Bone Marrow Failure Disorders
• Bone Marrow Failure Syndrome
• Chronic Myeloid Leukemia
• Cytopenia
• Epstein-Barr Virus Infections
• Hemoglobinopathies
• Hemophagocytic Lymphohistiocytoses
• Immunologic Deficiency Syndromes
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphohistiocytosis, Hemophagocytic
• Myelodysplastic Syndromes
• Pancytopenia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Primary Immunodeficiency Diseases
• Severe Aplastic Anemia
• Syndrome
• Virus Diseases

• NCT number: NCT05236764
• Study type: Interventional
• Source: Baylor College of Medicine
• Contact: Erin Morales, MD
• Phone: 832-826-0860
• Email: erin.moralesubico@bcm.edu
• Status: Recruiting
• Phase: N/A
• Start date: December 6, 2023
• Completion date: August 1, 2030