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NCT04806347 | Not yet recruiting | Blood Disease

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

University of Wisconsin, Madison

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.

Condition or disease

Blood Disease


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

CliniMACS® System


Phase 1

Study Type : Interventional
Estimated Enrollment : 12 participants
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2023
Estimated Primary Completion Date : March 2028
Estimated Study Completion Date : March 2029
Arm Intervention/treatment

Experimental: 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.

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

Device: CliniMACS® System

Ages Eligible for Study: 3 Months to 40 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
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).

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

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

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