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

NCT05236764 | Active Not Recruiting Results DMC FDA Device

• 1 other identifier: H-50045 HAPLOTAB
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Myelodysplastic Syndromes; Chronic Myeloid Leukemia; Hemophagocytic Lymphohistiocytoses; Primary Immunodeficiency Diseases; Hemoglobinopathies; Severe Aplastic Anemia; Cytopenia; Bone Marrow Failure Syndrome; Severe Chronic Active Epstein-Barr Virus Infection

Keywords

Stem Cell Transplant; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Myelodysplastic Syndromes; Non-Hodgkins Lymphoma; Chronic Myeloid Leukemia; Hemophagocytic Lymphohistiocytoses; Primary Immunodeficiency Diseases; Hemoglobinopathies; Severe Aplastic Anemia; Congenital/hereditary cytopenias including Fanconi Anemia; Bone Marrow Failure Syndrome; Severe Chronic active Epstein-Barr Virus Infections

Outcome Measures

Primary Outcomes (2)

• Cumulative Incidence of Neutrophil Engraftment and Platelet Engraftment

  Cumulative incidence of neutrophil and platelet engraftment (composite measure) will be reported as rate and its associated 95% confidence interval. Competing risks methods will be utilized, with graft failure and death considered as competing risks. Neutrophil engraftment is defined as the first of 3 consecutive days with a peripheral blood absolute neutrophil count of ≥ 0.5x10\^9/L Platelet engraftment is defined as the first day with platelet count of ≥ 20 x10\^9/L without transfusion support for 7 consecutive days

  42 days post-HCT

• Cumulative Incidence of Grade III or Higher Acute GVHD

  Cumulative incidence of grade III or higher acute GVHD among patients who achieve engraftment will be reported as rate and its associated 95% confidence interval. Competing risks methods will be utilized, with death considered the competing risk.

  100 days post-HCT

Secondary Outcomes (3)

• Cumulative Incidence of Transplant-related Mortality (TRM)

  100 days and 365 days post-HCT

• Overall Survival (OS)

  Up to one year post-HCT

• Cumulative Incidence of Chronic Graft Versus Host Disease

  Up to two years post HCT

Study Arms (1)

Alpha beta+ T cell depleted CD34+ stem cells

EXPERIMENTAL

The patient will be receiving a donor stem cell transplant with a preceding conditioning regimen (chemotherapy with, or without, radiation). The investigators will be specially treating the donor's blood cells used for the stem cell transplant.

Device: CliniMACS

Interventions

CliniMACS DEVICE

Peripheral blood stem cells from closely matched unrelated donors will be processed using the CliniMACS device to remove TCRalpha/beta (alpha beta+) T cells and B cells, in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique

Alpha beta+ T cell depleted CD34+ stem cells

Eligibility Criteria

• Age: Up to 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Lack of suitable conventional donor (10/10 HLA matched related or unrelated donor) or presence of rapidly progressive disease not permitting time to identify an HLA-matched unrelated donor. This does not include cord blood unit (CBU) availability.
• Lansky/Karnofsky score \> 50
• Signed written informed consent
• Diagnosis of one of the following:
• Patient with life threatening hematological malignancy including "high-risk" ALL in first complete remission (CR1); ALL in second or subsequent remission (greater than or equal to CR2); high-risk AML in CR1; AML in second or subsequent CR; myelodysplastic syndromes (MDS); non-Hodgkin's lymphomas (NHL) in second or subsequent remission (greater than or equal to CR2); CML
• Hemophagocytic Lymphohistiocytosis (HLH) including familial HLH, relapsed HLH or central nervous system (CNS) HLH
• Primary Immunodeficiency Disorders (PID)
• Hemoglobinopathies including thalassemia or sickle cell disease (SCD)
• Severe aplastic anemia (SAA) not responding to immune suppressive therapy
• Congenital/hereditary cytopenias including Fanconi anemia (FA) without malignant clonal evolution (MDA, AML)
• Other inherited bone marrow failure syndromes (IBMFS)
• Sever chronic active Epstein Barr virus infection (SCAEBV) with predilection for T-or NK-cell malignancy
• NOTE: 'High risk' ALL or AML refers to those acute leukemias identified by the presence of specific biologic features, which predict high likelihood of failure to conventional chemotherapy. As biologic features of high-risk disease evolve with improvement of conventional chemotherapy, it is not practical to define this indication with any further specificity. Therefore, high risk AML/ALL will be determined by the primary physician.

You may not qualify if:

• Life expectancy of less than or equal to 6 weeks
• Symptomatic cardiac disease or left ventricular shortening fraction less than 25% or ejection fraction \< 40%
• Severe renal disease, with creatinine clearance \< 40cc/1.73m2
• Pre-existing severe restrictive pulmonary disease, FVC \< 40% of predicted
• Severe Hepatic Disease with ALT/AST ≥ x 2.5 upper limit of normal or bilirubin level ≥ x 1.5 upper limit of normal
• Serious concurrent uncontrolled medical disorder or mental illness
• Pregnant or breastfeeding female subject
• Current active infectious disease including viral and fungal diseases at the time of enrollment; that on evaluation of PI precludes ablative chemotherapy or successful transplantation
• Active HIV infection
• Severe personality disorder or mental illness that would preclude compliance with the study

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphohistiocytosis, Hemophagocytic; Primary Immunodeficiency Diseases; Hemoglobinopathies; Anemia, Aplastic; Cytopenia; Bone Marrow Failure Disorders; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Anemia; Leukemia, Lymphoid; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma

Results Point of Contact

• Title: Dr. Erin Morales
• Organization: Baylor College of Medicine

erin.moralesubico@bcm.edu

832-826-0860

Study Officials

• Erin Morales, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 2, 2022
• First Posted: February 11, 2022
• Study Start: December 6, 2023
• Primary Completion: August 29, 2024
• Study Completion: May 23, 2026
• Last Updated: October 30, 2025
• Results First Posted: October 30, 2025

Record last verified: 2025-09

Locations

US (2)