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

Primary Purpose

Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia in Remission, Myelodysplastic Syndromes

Status

Not yet recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

CliniMACS

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia in Remission focused on measuring 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

Eligibility Criteria

undefined - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 dono. This does not include cord blood unit (CBU) availability.
Lansky/Karnofsky score > 50
Signed written informed consent
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:

Life expectancy of less than or equal to 6 weeks
Greater than grade II acute graft versus host disease (GVHD) or chronic extensive GVHD due to a previous allograft at the time of inclusion
Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous allograft at the time of inclusion
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 > x5 upper limit of normal or bilirubin level > x3 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

Sites / Locations

Houston Methodist Hospital
Texas Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Alpha beta+ T cell depleted CD34+ stem cells

Arm Description

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.

Outcomes

Primary Outcome Measures

Rate of neutrophil engraftment

Neutrophil engraftment defined as the first of 3 consecutive days with a peripheral blood absolute neutrophil count of ≥ 0.5x10^9/L

Rate of platelet engraftment

Platelet engraftment defined as the first day with platelet count of ≥ 20 x10^9/L without transfusion support for 7 consecutive days

Rate of acute graft versus host disease (GvHD) by grades

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

Rate of transplant-related mortality (TRM)

Defined as death due to any transplantation-related cause, other than disease

Overall survival (OS)

The length of time from the day of transplant to death

Full Information

NCT ID

NCT05236764

First Posted

February 2, 2022

Last Updated

August 15, 2023

Sponsor

Baylor College of Medicine

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT05236764

Brief Title

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

Acronym

HAPLOTAB

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 2023 (Anticipated)

Primary Completion Date

October 2026 (Anticipated)

Study Completion Date

August 1, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Baylor College of Medicine

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

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.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

47 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Alpha beta+ T cell depleted CD34+ stem cells

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

CliniMACS

Intervention Description

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 Measure Information:

Title

Rate of neutrophil engraftment

Description

Neutrophil engraftment defined as the first of 3 consecutive days with a peripheral blood absolute neutrophil count of ≥ 0.5x10^9/L

Time Frame

42 days post-HCT

Title

Rate of platelet engraftment

Description

Platelet engraftment defined as the first day with platelet count of ≥ 20 x10^9/L without transfusion support for 7 consecutive days

Time Frame

42 days post-HCT

Title

Rate of acute graft versus host disease (GvHD) by grades

Description

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

Time Frame

100 days post-HCT

Secondary Outcome Measure Information:

Title

Rate of transplant-related mortality (TRM)

Description

Defined as death due to any transplantation-related cause, other than disease

Time Frame

100 days and 365 days post-HCT

Title

Overall survival (OS)

Description

The length of time from the day of transplant to death

Time Frame

Up to one year post-HCT

10. Eligibility

Sex

All

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: Life expectancy of less than or equal to 6 weeks Greater than grade II acute graft versus host disease (GVHD) or chronic extensive GVHD due to a previous allograft at the time of inclusion Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous allograft at the time of inclusion 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Bahey Salem, MD

Phone

832-824-1803

bmsalem@texaschildrens.org

First Name & Middle Initial & Last Name or Official Title & Degree

Martha Arredondo

Phone

832-824-1201

Martha.Arredondo@bcm.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bahey Salem, MD

Organizational Affiliation

Baylor College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Houston Methodist Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

George Carrum, MD

Phone

713-441-1450

gcarrum@bcm.edu

First Name & Middle Initial & Last Name & Degree

Martha Arredondo

Phone

832-824-1201

Martha.Arredondo@bcm.edu

Facility Name

Texas Children's Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Salem Bahey, MD

Phone

832-824-1803

bmsalem@texaschildrens.org

First Name & Middle Initial & Last Name & Degree

Martha Arredondo

Phone

832-824-1201

Martha.Arredondo@bcm.edu

12. IPD Sharing Statement

Learn more about this trial

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

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