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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndromes; Primary Immunodeficiency Diseases; Hemoglobinopathies; Chronic Myeloid Leukemia; Cytopenia; Severe Aplastic Anemia; Bone Marrow Failure Syndrome; Acute Myeloid Leukemia in Remission; Hemophagocytic Lymphohistiocytoses; Acute Lymphoblastic Leukemia in Remission; Severe Chronic Active Epstein-Barr Virus Infection
• Intervention / Treatment: Device: CliniMACS

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 55 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidence of Transplant-related Mortality (TRM)	Cumulative incidence of transplant related mortality will be reported as rate and its associated 95% confidence interval. TRM is defined as death due to any transplantation-related cause, other than disease	100 days and 365 days post-HCT
Overall Survival (OS)	The length of time from the day of transplant to death	Up to one year post-HCT
Cumulative Incidence of Chronic Graft Versus Host Disease	Cumulative incidence of chronic GVHD among patients who achieve engraftment will be reported as rate of chronic GvHD and its associated 95% confidence interval.	Up to two years post HCT

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: The Methodist Hospital Research Institute; Center for Cell and Gene Therapy, Baylor College of Medicine
• Investigators: Principal Investigator: Erin Morales, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2023
• Primary Completion (Actual): August 29, 2024
• Study Completion (Estimated): May 23, 2026

Study Registration Dates

• First Submitted: February 2, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Estimated): October 30, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Chronic Myeloid Leukemia; Stem Cell Transplant; Non-Hodgkins Lymphoma; Severe Aplastic Anemia; Hemophagocytic Lymphohistiocytoses; Hemoglobinopathies; Primary Immunodeficiency Diseases; Congenital/hereditary cytopenias including Fanconi Anemia; Bone Marrow Failure Syndrome; Severe Chronic active Epstein-Barr Virus Infections
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Genetic Diseases, Inborn; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Immunologic Deficiency Syndromes; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Leukemia, Myeloid; Bone Marrow Diseases; Anemia; Leukemia, Lymphoid; Leukemia; Myeloproliferative Disorders; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Primary Immunodeficiency Diseases; Bone Marrow Failure Disorders; Cytopenia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Anemia, Aplastic; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hemoglobinopathies; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: H-50045 HAPLOTAB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No