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

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ClinicalTrials.gov Identifier: NCT05236764
Recruitment Status : Not yet recruiting
First Posted : February 11, 2022
Last Update Posted : December 12, 2022
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital Research Institute
Information provided by (Responsible Party):
Bahey Salem MD, Baylor College of Medicine

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.

Condition or disease Intervention/treatment Phase
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 Device: CliniMACS Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : March 7, 2023
Estimated Primary Completion Date : November 10, 2025
Estimated Study Completion Date : August 1, 2030

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

Primary Outcome Measures :
  1. Rate of neutrophil engraftment [ Time Frame: 42 days post-HCT ]
    Neutrophil engraftment defined as the first of 3 consecutive days with a peripheral blood absolute neutrophil count of ≥ 0.5x10^9/L

  2. Rate of platelet engraftment [ Time Frame: 42 days post-HCT ]
    Platelet engraftment defined as the first day with platelet count of ≥ 20 x10^9/L without transfusion support for 7 consecutive days

  3. Rate of acute graft versus host disease (GvHD) by grades [ Time Frame: 100 days post-HCT ]
    Number of patients who developed grade III or higher aGvHD among patients who achieve engraftment will be reported as rate of acute GvHD and its associated 95% confidence interval

Secondary Outcome Measures :
  1. Rate of transplant-related mortality (TRM) [ Time Frame: 100 days and 365 days post-HCT ]
    Defined as death due to any transplantation-related cause, other than disease

  2. Overall survival (OS) [ Time Frame: Up to one year post-HCT ]
    The length of time from the day of transplant to death

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05236764

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Contact: Bahey Salem, MD 832-824-1803 bmsalem@texaschildrens.org
Contact: Martha Arredondo 832-824-1201 Martha.Arredondo@bcm.edu

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United States, Texas
Houston Methodist Hospital
Houston, Texas, United States, 77030
Contact: George Carrum, MD    713-441-1450    gcarrum@bcm.edu   
Contact: Martha Arredondo    832-824-1201    Martha.Arredondo@bcm.edu   
Texas Children's Hospital
Houston, Texas, United States, 77030
Contact: Salem Bahey, MD    832-824-1803    bmsalem@texaschildrens.org   
Contact: Martha Arredondo    832-824-1201    Martha.Arredondo@bcm.edu   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital Research Institute
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Principal Investigator: Bahey Salem, MD Baylor College of Medicine
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Responsible Party: Bahey Salem MD, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT05236764    
Other Study ID Numbers: H-50045 HAPLOTAB
First Posted: February 11, 2022    Key Record Dates
Last Update Posted: December 12, 2022
Last Verified: December 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Bahey Salem MD, Baylor College of Medicine:
Stem Cell Transplant
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Non-Hodgkins Lymphoma
Chronic Myeloid Leukemia
Hemophagocytic Lymphohistiocytoses
Primary Immunodeficiency Diseases
Severe Aplastic Anemia
Congenital/hereditary cytopenias including Fanconi Anemia
Bone Marrow Failure Syndrome
Severe Chronic active Epstein-Barr Virus Infections
Additional relevant MeSH terms:
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Virus Diseases
Epstein-Barr Virus Infections
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Anemia, Aplastic
Bone Marrow Failure Disorders
Lymphohistiocytosis, Hemophagocytic
Primary Immunodeficiency Diseases
Immunologic Deficiency Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders