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

NCT ID: NCT05236764

Last Updated: 2025-10-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-06
• Study Completion Date: 2026-05-23

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.

Detailed 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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Alpha beta+ T cell depleted CD34+ stem cells

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.

Group Type: EXPERIMENTAL

CliniMACS

Intervention Type: 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

Interventions

CliniMACS

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Lansky/Karnofsky score > 50

3. Signed written informed consent

4. Diagnosis of one of the following:

1. 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

2. Hemophagocytic Lymphohistiocytosis (HLH) including familial HLH, relapsed HLH or central nervous system (CNS) HLH

3. Primary Immunodeficiency Disorders (PID)

4. Hemoglobinopathies including thalassemia or sickle cell disease (SCD)

5. Severe aplastic anemia (SAA) not responding to immune suppressive therapy

6. Congenital/hereditary cytopenias including Fanconi anemia (FA) without malignant clonal evolution (MDA, AML)

7. Other inherited bone marrow failure syndromes (IBMFS)

8. 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.

Exclusion Criteria

1. Life expectancy of less than or equal to 6 weeks

2. Greater than grade II acute graft versus host disease (GVHD) or chronic extensive GVHD due to a previous allograft at the time of inclusion

3. Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous allograft at the time of inclusion

4. Symptomatic cardiac disease or left ventricular shortening fraction less than 25% or ejection fraction < 40%

5. Severe renal disease, with creatinine clearance < 40cc/1.73m2

6. Pre-existing severe restrictive pulmonary disease, FVC < 40% of predicted

7. Severe Hepatic Disease with ALT/AST ≥ x 2.5 upper limit of normal or bilirubin level ≥ x 1.5 upper limit of normal

8. Serious concurrent uncontrolled medical disorder or mental illness

9. Pregnant or breastfeeding female subject

10. 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

11. Active HIV infection

12. Severe personality disorder or mental illness that would preclude compliance with the study

• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Center for Cell and Gene Therapy, Baylor College of Medicine

OTHER

Sponsor Role: collaborator

The Methodist Hospital Research Institute

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Erin Morales

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Erin Morales, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Houston Methodist Hospital

Houston, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

H-50045 HAPLOTAB

Identifier Type: -

Identifier Source: org_study_id