Alpha/Beta T-cell Depleted Blood-forming Stem Cell Transplant From Related or Unrelated Donors for Blood Diseases in Children and Young Adults

NCT ID: NCT04806347

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-04-30
• Study Completion Date: 2030-05-31

Brief Summary

This single institution, phase I clinical trial will determine the safety and feasibility of employing T-cell receptor (TCR) αβ+ and CD19+ (Cluster of Differentiation ) depleted hematopoietic stem cell transplantation (HSCT) using peripheral blood stem cells (PBMC) from closely matched unrelated donors or haploidentical donors to treat non-malignant hematologic diseases in children and young adults. Allogeneic hematopoietic stem cell transplantation has become a curative option for children and adolescents with a variety of otherwise fatal conditions. To reduce the incidence and severity of graft-versus-host disease (GVHD) associated with allogeneic hematopoietic stem cell transplantation, donor grafts are depleted of T cells, either using CD34+ selection or CD3+/CD19+ depletion of grafts. However, these selection processes also deplete the graft of protective cell subsets, such as γδ T cells, natural killer(NK) cells, monocytes and dendritic cells, which play important roles in the immune response to infectious agents. Moreover, the presence of NK cells and γδ T in donor grafts is associated with more rapid immune reconstitution after HSCT transplantation. In order to retain these protective immune cell subsets, this trial will use a novel, highly selective graft engineering process using the Miltenyi CliniMACS system that selectively depletes αβ-T cells and B cells which are responsible for GVHD and Epstein Barr Virus (EBV)-related post-transplantation lymphoproliferative disorder, respectively. Prior to transplantation, patients will be treated with a conditioning regimen, specific for the original disorder. The primary objective of this study is evaluation of the safety and feasibility of HSCT using TCRαβ+/CD19+ depleted hematopoietic stem cells to treat non-malignant hematologic diseases. This will be assessed by evaluating the incidence of graft failure, grade III-IV acute GVHD and chronic GVHD and TRM. Secondary objectives include the evaluation of immune reconstitution and incidence of post-transplant infections, adverse events, serious adverse events, overall and disease-free survival and the efficiency of graft processing by the CliniMACS System.

Conditions

Blood Disease

Study Design

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

Study Groups

Treatment arm

Participants will undergo a conditioning regimen, specific for the original disease, After that peripheral blood stem cell transplant from a haploidentical donor or closely matched unrelated donor, depleted of TCRαβ+ and CD19+ cells using the CliniMACS TCR α/β-biotin and CD19 Systems will be administered intravenously on Day 0 to all participants.

Group Type: EXPERIMENTAL

TCRαβ+/CD19+ depleted Hematopoietic stem cell (HSC) graft

Intervention Type: BIOLOGICAL

After undergoing a disease specific conditioning regimen (standard of care), participants will receive peripheral blood stem cell transplant from a haploidentical donor or closely matched unrelated donor, depleted of TCR αβ+ and CD19+ cells using the CliniMACS TCR α/β-biotin and CD19 Systems.

CliniMACS® System

Intervention Type: DEVICE

The CliniMACS Cell Selection System is based on magnetic-activated cell sorting mechanism. The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures.

Interventions

TCRαβ+/CD19+ depleted Hematopoietic stem cell (HSC) graft

After undergoing a disease specific conditioning regimen (standard of care), participants will receive peripheral blood stem cell transplant from a haploidentical donor or closely matched unrelated donor, depleted of TCR αβ+ and CD19+ cells using the CliniMACS TCR α/β-biotin and CD19 Systems.

Intervention Type: BIOLOGICAL

CliniMACS® System

The CliniMACS Cell Selection System is based on magnetic-activated cell sorting mechanism. The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• No Human leukocyte antigen (HLA) identical sibling available AND
• NO HLA matched unrelated donor available OR urgent need of HSCT precludes time necessary to search for suitable HLA matched unrelated donor AND
• Haploidentical donor OR closely matched unrelated donor available and willing to undergo mobilization and apheresis
• If subject has genetically confirmed inherited bone marrow failure, related donor must be evaluated for this disorder and testing must be negative.
• If subject has sickle cell disease, donor may have only sickle cell trait
• Patient must be diagnosed with one of the following diseases or disorders:

Hemoglobinopathies

• Sickle Cell Disease for patients ≤ 21 years of age for whom hydroxyurea has been trialed for at least six months, and failed
• Thalassemia Major for patients ≤ 21 years of age

Acquired Bone Marrow Failure Syndromes

• Paroxysmal Nocturnal Hemoglobinuria with bone marrow failure
• Myelodysplastic Syndromes (lower risk)

Inherited Bone Marrow Failure Syndromes

• Fanconi Anemia
• Diamond Blackfan Anemia
• Dyskeratosis Congenita and related telomere disorders
• Congenital Thrombocytopenia Syndromes
• Severe Congenital Neutropenia
• Shwachman-Diamond Syndrome
• Age ≤ 40 years (except patients with hemoglobinopathies)
• Life Expectancy ≥ 3 months
• Karnofsky (patients > 16 years)/Lansky (patients ≤ 16 years) index ≥ 60
• Organ Function Requirements

Renal Function

• Creatinine clearance or radioisotope Glomerular Filtration Rate (GFR) greater than or equal to 60 ml/min/1.73m^2

Liver Function

• Total bilirubin < 3 mg/dL
• Alanine aminotransferase (ALT)/ Serum glutamic-pyruvic transaminase; synonymous with ALT (SCPT) ≤ 3 x Upper Limit of Normal(ULN) for age

Cardiac Function

• Ejection fraction of > 40% by Multiple gated acquisition scan (MUGA) or echocardiogram

Pulmonary Function

• No evidence of dyspnea at rest
• No supplemental oxygen requirement
• If measured, carbon monoxide diffusion capacity (DLCO) > 50%
• Willing to use effective birth control method if patient is of reproductive potential
• Informed consent obtained (patient or legal representative)

Exclusion Criteria

• Pregnant
• HIV infection
• Uncontrolled, serious active infection at screening
• Significant serious intercurrent illnesses
• Enrollment in any other treatment study that would interfere with the endpoints of this study according to judgement of Principal Investigator(or PI designee).

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Capitini, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Jacques Galipeau, MD

Role: STUDY_DIRECTOR

University of Wisconsin, Madison

Central Contacts

Jenny Weiland

Role: CONTACT

PedsHemOncResearch@lists.wisc.edu

608-890-8070

Celeste Matsushima

Role: CONTACT

608-890-8069

Other Identifiers

2020-1251

Identifier Type: OTHER

Identifier Source: secondary_id

A536755

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 4

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2021-02128

Identifier Type: REGISTRY

Identifier Source: secondary_id

UW19113

Identifier Type: -

Identifier Source: org_study_id