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

January 16, 2024 updated by: Erin Morales, Baylor College of Medicine

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

Recruiting

Conditions

Intervention / Treatment

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 (Estimated)

47

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
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
42 days post-HCT
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
42 days post-HCT
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
100 days post-HCT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
100 days and 365 days post-HCT
Overall survival (OS)
Time Frame: Up to one year post-HCT
The length of time from the day of transplant to death
Up to one year post-HCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 6, 2023

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

August 1, 2030

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)

January 18, 2024

Last Update Submitted That Met QC Criteria

January 16, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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