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Transplantatie van alfa-/bèta-T-cellen met bloedvormende stamcellen van verwante of niet-verwante donoren voor bloedziekten bij kinderen en jongvolwassenen

28 oktober 2026 bijgewerkt door: University of Wisconsin, Madison

TCRαβ+ en CD19+ verarmde hematopoëtische stamceltransplantatie van nauw op elkaar afgestemde niet-verwante donoren of haplo-identieke verwante donoren voor hematologische aandoeningen bij kinderen en jongvolwassenen

This study is being done to see if the investigators can take peripheral blood stem cells from either an adult family member or a closely matched unrelated donor, and run them through a special lab instrument to remove alpha/beta T cells and B cells and then give them to the patient to treat disease. This is an experimental way of doing a hematopoietic stem cell transplant (HSCT). The investigators want to see if the new stem cells will grow without bad graft vs. host disease (GVHD). This treatment approach is experimental in the United States.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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 cells 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 that 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.

Studietype

Ingrijpend

Inschrijving (Geschat)

12

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

  • Naam: Celeste Matsushima
  • Telefoonnummer: 608-890-8069

Studie Contact Back-up

Studie Locaties

  • Verenigde Staten
    • Wisconsin
      • Madison, Wisconsin, Verenigde Staten, 53792
        • Werving
        • American Family Children's Hospital

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

3 maanden tot 25 jaar (Kind, Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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 must be unaffected or 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)
      • Severe acquired aplastic anemia

    • 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

    • Inborn Errors of Immunity (IEI) or Primary Immune Regulatory Disorders (PIRD)

      • Wiskott-Aldrich syndrome (WAS)
      • Chronic granulomatous disease (CGD)
      • Severe combined immunodeficiency (SCID)
      • Primary hemophagocytic lymphohistiocytosis (HLH)

  • Age ≤ 25 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).

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Biologisch: 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.

Apparaat: 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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Incidence of grade III-IV acute graft-versus-host disease (GVHD)
Tijdsspanne: 100 days post transplantation

Acute GVHD will be assessed and graded according to the Keystone Consensus Criteria for staging and grading of acute graft-versus-host disease.
100 days post transplantation
Incidence of extensive chronic GVHD
Tijdsspanne: up to 2 years

Chronic GVHD will be assessed according to the current CIBMTR (Center for International Blood and Marrow Transplant Research) manual reflecting a grading system published by Sullivan KM (Sullivan 1981).
up to 2 years
Incidence of graft failure
Tijdsspanne: up to 2 years after graft

Graft failure - defined as failure to achieve ANC > 500 /µL at Day +28 or initial neutrophil engraftment followed by a decline in ANC < 500 /µL that is unresponsive to growth factor therapy (secondary graft failure).
up to 2 years after graft
Incidence of Treatment Related Mortality (TRM)
Tijdsspanne: Day +100 post-HSCT

TRM - defined as death from any cause other than disease progression.
Day +100 post-HSCT

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Algehele overleving (OS)
Tijdsspanne: tot 2 jaar
tot 2 jaar
CliniMACS-systeemefficiëntie: Percentage levensvatbare CD34+-cellen hersteld na de TCRαβ+- en CD19+-depletieprocedure
Tijdsspanne: tot 12 maanden na HSCT
tot 12 maanden na HSCT
Correlatie tussen GVHD-incidentie en haplotype-inhoud van donor-killer-cel immunoglobuline-achtige receptor (KIR)
Tijdsspanne: tot 2 jaar
tot 2 jaar
Correlatie tussen GVHD-incidentie en killer-cel immunoglobuline-achtige receptor (KIR) / KIR-ligand-mismatch tussen donor en ontvanger.
Tijdsspanne: tot 2 jaar
tot 2 jaar
Aantal deelnemers met bijwerkingen gerelateerd aan infusie van het HSC-transplantaat
Tijdsspanne: Dag 0
Dag 0
Incidentie van ernstige bijwerkingen
Tijdsspanne: tot 2 jaar
tot 2 jaar
CliniMACS system efficiency: log depletion value for CD19/CD20+ B cells after the TCRαβ+ and CD19+ depletion procedure
Tijdsspanne: Day 0
Day 0
CliniMACS system efficiency: log depletion value of TCRαβ+ T cells after the TCRαβ+ and CD19+ depletion procedure
Tijdsspanne: Day 0
Day 0
Time to neutrophil engraftment
Tijdsspanne: up to 28 days following HSCT

The time to neutrophil engraftment is defined as the post-transplant day that is the first of 3 consecutive days with an absolute neutrophil count (ANC) of >500/µL as assessed by CBC.
up to 28 days following HSCT
Time to platelet engraftment
Tijdsspanne: up to 28 days following HSCT

The time to platelet engraftment is defined as the post-transplant day that is the first of 3 consecutive days with a platelet count ≥ 20,000/µL as assessed by complete blood count (CBC), without platelet support (transfusion) for 7 days.
up to 28 days following HSCT
Percentage donor chimerism using Short Tandem Repeat (STR)
Tijdsspanne: up to 12 months following HSCT

Short tandem repeat (STR) analysis will provide the percentage donor chimerism at specific time points post-transplant.
up to 12 months following HSCT
Kinetics of lymphocyte reconstitution via immunophenotyping using flow cytometry
Tijdsspanne: up to 12 months following HSCT

Lymphocyte reconstitution will be assessed at specific time points post-HSCT, expressed as the percentage of white blood cells comprised of T, B and NK cell subsets.
up to 12 months following HSCT
CliniMACS system efficiency: number of viable blood cell subsets after the TCRαβ+ and CD19+ depletion procedure
Tijdsspanne: Day 0

Number of viable CD34+ blood stem cells, CD20+ B cells, CD3-CD56+ NK cells, TCRαβ+ T cells, and TCRγδ+ T cells in the HSC graft after the TCRαβ+ and CD19+ depletion procedure
Day 0
Event free survival
Tijdsspanne: up to 1 years

An event is defined as death, graft failure or stable mixed chimerism with disease recurrence.
up to 1 years
Incidence of symptomatic bacterial/fungal and viral reactivation requiring therapy
Tijdsspanne: up to 1 year

The incidence of infections (symptomatic bacterial/fungal and viral reactivation requiring therapy) will be used as an additional safety measure
up to 1 year

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

University of Wisconsin, Madison

Onderzoekers

  • Hoofdonderzoeker: Christian Capitini, MD, University of Wisconsin, Madison
  • Studie directeur: Jacques Galipeau, MD, University of Wisconsin, Madison

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 november 2026

Primaire voltooiing (Geschat)

1 juni 2029

Studie voltooiing (Geschat)

1 juni 2030

Studieregistratiedata

Eerst ingediend

2 maart 2021

Eerst ingediend dat voldeed aan de QC-criteria

16 maart 2021

Eerst geplaatst (Werkelijk)

19 maart 2021

Updates van studierecords

Laatste update geplaatst (Werkelijk)

29 oktober 2026

Laatste update ingediend die voldeed aan QC-criteria

28 oktober 2026

Laatst geverifieerd

1 september 2026

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 2020-1251
  • A536755 (Andere identificatie: UW Madison)
  • UW19113 (Andere identificatie: OnCore ID)
  • 2020-1251 (Andere identificatie: HS IRB UW Madison)
  • NCI-2021-02128 (Register-ID: NCI CTRP)
  • Protocol Version 6 (Andere identificatie: HS-IRB UW Madison)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

The Principal Investigator, Sponsor and funding institutions (if applicable) will ensure that all mechanisms used to share data include proper plans and safeguards to protect the rights and privacy of participants who participate in this research.

IPD delen Ondersteunend informatietype

  • LEERPROTOCOOL
  • SAP

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Ja

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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