PRIMARY OBJECTIVE:
I. To evaluate 1-year event-free survival (EFS) from the time of SJCARB7H3_41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate the overall survival (OS) from time of SJCARB7H3_41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy.
II. To evaluate the feasibility of delivering SJCARB7H3_41BBL at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma.
III. To describe the safety of autologous SJCARB7H3_41BBL therapy when delivered at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma.
EXPLORATORY OBJECTIVES:
I. To characterize the tumor genomics, methylation, and tumor B7-H3 antigen expression and describe the relationship between EFS and toxicity.
II. To determine if SJCARB7H3_41BBL traffic to pulmonary osteosarcoma metastatic sites.
III. For those receiving Regimen A, to describe the timing of pulmonary metastasectomy following SJCARB7H3_41BBL infusion and associated adverse events related to pulmonary metastasectomy.
IV. To measure circulating cell-free DNA to quantify both tumor and SJCARB7H3_41BBL DNA through the course of protocol treatment and correlate with the presence of SJCARB7H3_41BBL detected by flow cytometry.
V. To characterize systemic immune profile, including endogenous T cell repertoires and cytokine analysis through the course of protocol therapy and follow-up, and describe the relationship to EFS and toxicity.
VI. To evaluate the local tumor microenvironment and adjacent normal tissue from archival primary tumor tissue and resected pulmonary metastatic lesions in response to SJCARB7H3_41BBL therapy and describe the relationship to EFS and toxicity.
VII. To compare expansion, persistence, immunophenotype, and functional status of SJCARB7H3_41BBL cells to similar data from other SJCARB7H3_41BBL trials performed at St. Jude.
OUTLINE: Patients are initially assigned to 1 of 2 regimens.
REGIMEN A:
INDUCTION: Patients receive standard of care (SOC) neoadjuvant chemotherapy with cisplatin and doxorubicin on weeks 0 and 5 and methotrexate on weeks 3, 4, 8 and 9 in the absence of disease progression or unacceptable toxicity. Patients undergo apheresis over 3-8 hours followed by SOC surgery on week 10.
CONSOLIDATION: Patients receive SOC chemotherapy with cisplatin on weeks 12 and 17, doxorubicin on weeks 12, 17, and 22 and methotrexate on weeks 15, 16, 20, 21 and 30 and 31 in the absence of disease progression or unacceptable toxicity. Patients who do not experience progression after consolidation therapy receive SOC lymphodepleting chemotherapy with fludarabine intravenously (IV) on days -5 to -2, cyclophosphamide IV on days -3 and -2 and SJCARB7H3_41BBL IV over 30 minutes on day 0. After day 28, patients undergo pulmonary metastasectomy per SOC.
REGIMEN B:
INDUCTION: Patients receive SOC chemotherapy with cisplatin and doxorubicin on weeks 0 and 5 and methotrexate on weeks 3, 4, 8 and 9 in the absence of disease progression or unacceptable toxicity. Patients undergo apheresis over 3-8 hours followed by SOC surgery on week 10.
CONSOLIDATION: Patients receive SOC chemotherapy with cisplatin on weeks 12 and 17, doxorubicin on weeks 12, 17, and 22 and methotrexate on weeks 15, 16, 20, 21 and 30 and 31 in the absence of disease progression or unacceptable toxicity. Patients undergo pulmonary metastasectomy on week 33 per SOC. Starting on week 35, patients who do not experience progression after consolidation therapy receive SOC lymphodepleting chemotherapy with fludarabine IV on days -5 to -2, cyclophosphamide IV on days -3 and -2 and SJCARB7H3_41BBL IV over 30 minutes on day 0.
Additionally, patients undergo echocardiography, positron emission tomography (PET), magnetic resonance imaging (MRI) or computed tomography (CT), chest CT, x-ray and blood sample collection throughout the study.
After completion of study treatment, patients are followed weekly through day 28, at 3, 6, 9, 12, 16, 20, and 24 months then for up to 15 years post-infusion.
