A Phase II Study Evaluating Efficacy of B7-H3-CAR T Cells Administered at the End of Upfront Map Chemotherapy in Patients With Newly Diagnosed High-Risk Osteosarcoma
Summary
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.
Detailed description
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\_41BBL product will receive lymphodepletion chemotherapy 14-28 days after the completion of standard chemotherapy (31 weeks after diagnosis), followed by SJCARB7H3\_41BBL infusion. If Regimen A is not cleared, then Regimen B will be evaluated, where lymphodepletion and SJCARB7H3\_41BBL 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\_41BBL 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.
Arms & interventions
- DrugCyclophosphamide
IV
- DrugFludarabine
IV
- DrugMesna
IV prior to and again at 3, 6, and 9 hours following each dose of cyclophosphamide.
- ProcedureApheresis
IV collection
- ProcedureSJCARB7H3_41BBL infusion
1X107 CAR+ T cells/kg
Outcome measures
Primary
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
Secondary
Overall survival (OS), defined as time from SJCARB7H3_41BBL cell infusion to all-cause mortality.
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.
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
Time frame: Time of SJCARB7H3_41BBL infusion
Eligibility criteria
Study locations (1)
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105-2794