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Evaluatie van de werkzaamheid van B7-H3-CAR T-cellen die aan het einde van de eerstelijns Map-chemotherapie worden toegediend aan patiënten met nieuw gediagnosticeerd hoog-risico osteosarcoom

2 november 2026 bijgewerkt door: St. Jude Children's Research Hospital

Een fase II-studie naar de effectiviteit van B7-H3-CAR T-cellen toegediend aan het einde van de initiële Map-chemotherapie bij patiënten met nieuw gediagnosticeerd hoog-risico osteosarcoom

The purpose of this study is to assess the safety, feasibility, and effectiveness of a consolidative B7-H3 CAR T cell therapy in patients with newly diagnosed high-risk osteosarcoma who have undergone upfront standard chemotherapy.

Primary Objectives:

- To evaluate 1-year RFS from the time of SJCARB7H3-41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy.

Secondary Objectives:

  • To evaluate the OS from time of SJCARB7H3-41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy.
  • To evaluate the feasibility of delivering SJCARB7H3-41BBL at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma.
  • To describe the safety of autologous SJCARB7H3-41BBL therapy when delivered at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

This is a phase 2 study of SJCARB7H3-41BBL for participants with newly diagnosed high-risk metastatic osteosarcoma who received standard chemotherapy.

All participants will receive standard chemotherapy (for example methotrexate, anthracycline, platinum), local control surgery, and pulmonary metastasectomy if applicable, and this is not considered part of protocol therapy. Participants will undergo apheresis prior to standard local control surgery (about 12 weeks after diagnosis) for SJCARB7H3-41BBL manufacture and then resume standard consolidation therapy. A safety run will initiate with Regimen A. For Regimen A, eligible participants with available SJCARB7H3-41BB product will receive lymphodepletion chemotherapy 14-28 days after the completion of standard chemotherapy (31 weeks after diagnosis), followed by SJCARB7H3-41BB infusion. If Regimen A is not cleared, then Regimen B will be evaluated, where lymphodepletion and SJCARB7H3-41BB infusion occur post pulmonary metastasectomy. Following successful clearance of either regimen A or, if necessary, regimen B, then the efficacy cohort will be initiated. Participants will be followed with serial disease evaluations for 2 years from SJCARB7H3-41BB infusion prior to transfer to our institutional long-term follow-up (LTFU) protocol. The total duration from completion of standard therapy, including experimental therapy and follow-up on 3CAR4OS, is approximately 2 years.

Studietype

Ingrijpend

Inschrijving (Geschat)

41

Fase

  • Fase 2

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

Studie Contact Back-up

Studie Locaties

  • Verenigde Staten
    • Tennessee
      • Memphis, Tennessee, Verenigde Staten, 38105-2794
        • Werving
        • St. Jude Children's Research Hospital
        • Hoofdonderzoeker:
          • Julie Park, MD
        • Contact:

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

Niet ouder dan 21 jaar (Kind, Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  1. Participant and/or legally authorized representative has signed the Informed Consent Form for this study

  2. Prior cancer therapy:

    • Regimen A only: Completed all planned cycles of consolidation therapy between 14-28 days prior.
    • Regimen B only: has completed all planned cycles of consolidation chemotherapy at least 14 days prior and if clinically indicated, participant has undergone pulmonary metastasectomy. They must have recovered from any surgical complications with no ongoing sequelae of category 2 or higher by the Clavien-Dindo classification system and less than 6 weeks must have passed from time of pulmonary metastasectomy.

  3. No evidence of progressive disease since enrolled on study

  4. Lansky performance status score of ≥ 50 for participants <16 years of age or Karnofsky score ≥ 50 for participants ≥ 16 years. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status

  5. Adequate organ function as indicated by:

    • Renal: Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) based on enrollment eligibility table.
    • Hepatic: Total bilirubin ≤ 3 times ULN for age OR conjugated bilirubin ≤ 2 mg/dL AND ALT (SGPT) ≤ 5 times ULN
    • Cardiac: Shortening fraction ≥ 28% OR ejection fraction ≥ 50% as measured by echocardiogram
    • Respiratory: Oxygen saturation ≥ 90% on room air without supplemental oxygen or mechanical ventilation

  6. Laboratory values meet the following criteria:

    • Absolute Neutrophil Count (ANC) ≥ 750 cells/uL
    • Platelet Count of ≥ 75,000 (can be transfused)
    • Hemoglobin ≥ 7 g/dL (can be transfused)

  7. Participant is ≥ 7 days from receiving supra-physiologic dosing of systemic (IV or PO) corticosteroids. Glucocorticosteroid physiologic replacement therapy for management of adrenal insufficiency is allowed.

  8. Participant and/or legally authorized representative has signed the Informed Consent Form for the treatment phase of this study.

Exclusion Criteria:

  1. Major surgical adverse event related to the primary tumor local control defined as Clavien-Dindo category 3 requiring ongoing wound care.

  2. Evidence of clinically significant encephalopathy/new focal neurologic deficits.

  3. Presence of active severe infection, defined as:

    • positive blood culture within 48 hours of enrollment, OR
    • fever above 38.2° C, AND clinical signs of infection within 48 hours of enrollment

  4. Participant has received prior disease-directed therapy other than 1st line therapy with methotrexate, an anthracycline, and a platinum and local control surgery

    • Regimen B only - okay to have undergone initial pulmonary metastasectomy

  5. Pregnant or breastfeeding

  6. Presence of any condition that, in the opinion of the investigator, would prohibit the participant from undergoing treatment under this protocol

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: 3CAR4OS Treatment

All patients will receive standard of care chemotherapy, which is not considered part of protocol therapy. Eligible patients will undergo apheresis prior to standard local control surgery for CAR T cell manufacture and then resume standard therapy. In the absence of progressive disease, eligible patients with available SJCARB7H3-41BBL product will receive lymphodepletion chemotherapy (fludarabine/cyclophosphamide) after the completion of standard chemotherapy, followed by SJCARB7H3-41BBL infusion. Pulmonary metastasectomy will be performed as indicated according to the standard of care and will be timed after (Regimen A) or before (Regimen B) lymphodepletion and SJCARB7H3-41BBL infusion. Following successful clearance of either regimen A or, if necessary, regimen B, the efficacy cohort will be initiated.
Geneesmiddel: Cyclophosphamide

IV

Geneesmiddel: Fludarabine

IV

Geneesmiddel: Mesna

IV prior to and again at 3, 6, and 9 hours following each dose of cyclophosphamide.

Procedure: Apheresis

IV collection

Procedure: SJCARB7H3_41BBL infusion

1X107 CAR+ T cells/kg

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Event-free survival (EFS), defined as time from SJCARB7H3-41BBL infusion to disease relapse, progressive disease, new systemic therapy, secondary malignancy or death
Tijdsspanne: Time from SJCARB7H3-41BBL infusion to time of first event, followed up to 24-months post-infusion

Event-free participants will be censored at the time of last follow-up. This analysis will report the Kaplan-Meier (KM) curve, along with the 12-month EFS estimate and its 80% confidence interval using the arcsine-square root transformation. Evaluable participants are those who complete standard chemotherapy, receive SJCARB7H3-41BBL and are treated on the regimen used for the Efficacy phase.
Time from SJCARB7H3-41BBL infusion to time of first event, followed up to 24-months post-infusion

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Overall survival (OS), defined as time from SJCARB7H3-41BBL cell infusion to all-cause mortality.
Tijdsspanne: Time from SJCARB7H3-41BBL infusion to time of death from any cause, followed up to 24-months post-infusion

Event-free participants will be censored at the time of last follow-up. OS will be reported similarly to the EFS endpoint on the same participant subset.
Time from SJCARB7H3-41BBL infusion to time of death from any cause, followed up to 24-months post-infusion
Number of participants experiencing protocol-specified regimen-related toxicities.
Tijdsspanne: Time from SJCARB7H3-41BBL infusion up to 28 days post-infusion.

This outcome measure will be descriptively summarized for the overall participant group and by regimen (if more than 1 regimen is evaluated) for each regimen-related toxicity. Evaluable participants include those who receive SJCARB7H3_41BBL and remain on protocol therapy through at least 28 days post-infusion or experience a related unacceptable toxicity.
Time from SJCARB7H3-41BBL infusion up to 28 days post-infusion.
Number of participants with successful manufacture of SJCARB7H3-41BBL cells of sufficient dose and planned product administration
Tijdsspanne: Time of SJCARB7H3-41BBL infusion

This outcome measure will be descriptively summarized for the overall participant group and by regimen (if more than 1 regimen is evaluated) for participants who undergo apheresis and remain on protocol therapy through the end of standard therapy.
Time of SJCARB7H3-41BBL infusion

Medewerkers en onderzoekers

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

Sponsor

St. Jude Children's Research Hospital

Onderzoekers

  • Hoofdonderzoeker: Julie Park, MD, St. Jude Children's Research Hospital

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Nuttige links

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 (Werkelijk)

21 augustus 2026

Primaire voltooiing (Geschat)

1 december 2034

Studie voltooiing (Geschat)

1 december 2035

Studieregistratiedata

Eerst ingediend

5 februari 2026

Eerst ingediend dat voldeed aan de QC-criteria

17 februari 2026

Eerst geplaatst (Werkelijk)

24 februari 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

3 november 2026

Laatste update ingediend die voldeed aan QC-criteria

2 november 2026

Laatst geverifieerd

1 november 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 3CAR4OS

Plan Individuele Deelnemersgegevens (IPD)

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

JA

Beschrijving IPD-plan

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

IPD-tijdsbestek voor delen

Data will be made available at the time of article publication.

IPD-toegangscriteria voor delen

Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

IPD delen Ondersteunend informatietype

  • LEERPROTOCOOL
  • SAP
  • ICF

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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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