A Phase 2 interventional study of Cyclophosphamide and Fludarabine in Pediatric Osteosarcoma, sponsored by St. Jude Children's Research Hospital. Recruiting at 1 site in United States. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2026-09-01.
Sponsored by St. Jude Children's Research Hospital · Phase 2, Interventional, and Treatment
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:
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.
Prior cancer therapy:
Adequate organ function as indicated by:
Laboratory values meet the following criteria:
Exclusion Criteria:
Presence of active severe infection, defined as:
Participant has received prior disease-directed therapy other than 1st line therapy with methotrexate, an anthracycline, and a platinum and local control surgery
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.
Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Mesna · Procedure: Apheresis · Procedure: SJCARB7H3_41BBL infusion
IV
IV
IV prior to and again at 3, 6, and 9 hours following each dose of cyclophosphamide.
IV collection
1X107 CAR+ T cells/kg
Event-free survival (EFS), defined as time from SJCARB7H3-41BBL infusion to disease relapse, progressive disease, new systemic therapy, secondary malignancy or death
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 frame: Time from SJCARB7H3-41BBL infusion to time of first event, followed up to 24-months post-infusion
Overall survival (OS), defined as time from SJCARB7H3-41BBL cell infusion to all-cause mortality.
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 frame: 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.
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 frame: 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
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 frame: Time of SJCARB7H3-41BBL infusion
Plan to share: Yes — 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.
Supporting information: Study protocol, Sap, Icf
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