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Évaluation de l'efficacité des cellules T CAR B7-H3 administrées à la fin de la chimiothérapie de première ligne Map chez les patients atteints d'ostéosarcome nouvellement diagnostiqué à haut risque

2 novembre 2026 mis à jour par: St. Jude Children's Research Hospital

Une étude de phase II évaluant l'efficacité des cellules T CAR B7-H3 administrées à la fin de la chimiothérapie d'induction chez les patients atteints d'ostéosarcome de haut risque nouvellement diagnostiqué

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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

41

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Lieux d'étude

  • États-Unis
    • Tennessee
      • Memphis, Tennessee, États-Unis, 38105-2794
        • Recrutement
        • St. Jude Children's Research Hospital
        • Chercheur principal:
          • Julie Park, MD
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

Pas plus vieux que 21 ans (Enfant, Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: Cyclophosphamide

IV

Médicament: Fludarabine

IV

Médicament: Mesna

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

Procédure: Apheresis

IV collection

Procédure: SJCARB7H3_41BBL infusion

1X107 CAR+ T cells/kg

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Event-free survival (EFS), defined as time from SJCARB7H3-41BBL infusion to disease relapse, progressive disease, new systemic therapy, secondary malignancy or death
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall survival (OS), defined as time from SJCARB7H3-41BBL cell infusion to all-cause mortality.
Délai: 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.
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

St. Jude Children's Research Hospital

Les enquêteurs

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

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

21 août 2026

Achèvement primaire (Estimé)

1 décembre 2034

Achèvement de l'étude (Estimé)

1 décembre 2035

Dates d'inscription aux études

Première soumission

5 février 2026

Première soumission répondant aux critères de contrôle qualité

17 février 2026

Première publication (Réel)

24 février 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

3 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

2 novembre 2026

Dernière vérification

1 novembre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 3CAR4OS

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

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.

Délai de partage IPD

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

Critères d'accès au partage IPD

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.

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE
  • CIF

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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