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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



Estimated Enrollment : 12 participants
Masking : NONE
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 : 2024-06
Estimated Primary Completion Date : 2028-03
Estimated Study Completion Date : 2029-03

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 3 Months to 40 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
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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