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NCT04806347

PHASE1

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

Sponsor: University of Wisconsin, Madison

View on ClinicalTrials.gov

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.

Official title: TCRαβ+ and CD19+ Depleted Hematopoietic Stem Cell Transplant From Closely Matched Unrelated Donors or Haploidentical Related Donors for Hematologic Diseases in Children and Young Adults

Key Details

Gender

All

Age Range

3 Months - 40 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2026-04

Completion Date

2030-05

Last Updated

2026-02-10

Healthy Volunteers

Conditions

Blood Disease

Interventions

BIOLOGICAL

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.

DEVICE

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.

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).