This is a phase I dose-escalation study to evaluate the safety of partially human leukocyte antigen (HLA)-matched multi tumor-associated antigen-specific T cell (TAA-T) therapy for patients with high-risk solid tumors due to the presence of refractory, relapsed and/or minimal residual detectable disease following conventional therapy. Conventional therapy may include chemotherapy, surgery, radiation, autologous stem cell transplant, or targeted therapy.
Diagnosis of high-risk solid tumors known to express at least 2 targeted antigens by either histology or historical reference: Ewing sarcoma, Wilms tumor, neuroblastoma, rhabdomyosarcoma, soft tissue sarcoma, and osteosarcoma.
HLA type and match through at least one allele with antigen-specific activity.
Refractory disease, residual detectable disease following conventional therapy or relapsed disease.
Arm A: age ≥18 years and <70 years
Patients with known human immunodeficiency virus (HIV) infection.
Pregnant or lactating females.
Patients who have undergone previous allogeneic stem cell transplant.
Patients who have undergone previous autologous stem cell transplant within the past 60 days.
Sequential
Tumor-associated antigen-specific T cell (TAA-T)
Biological/VaccinePatients will receive an infusion of partially HLA-matched TAA-T any time \>1 week after completing most recent course of conventional (non-investigational) therapy for their disease. For the lymphodepletion cohort, patients will receive lymphodepletion (LD) chemotherapy \>2 weeks from most recent course of conventional therapy and will nadir and recover before beginning TAA-T therapy. Patients will be enrolled to one of the following TAA-T dose levels: BSA \<1.20 BSA ≥1.20 Dose level 1 without LD (low dose) 2x107 cells 4x107 cells Dose level 2 (LD + Low dose) 2x107 cells 4x107 cells Dose level 3 (LD + High dose) 4x107 cells 8x107 cells
The rate of toxicities after TAA-T infusion
* Incidence of grades 3 to 5 infusion-related adverse event occurring within 45 days of the first TAA-T infusion. * Incidence of grades 4 to 5 non-hematologic adverse event related to TAA-T product occurring within 45 days of the first TAA-T infusion and that are not due to the patient's underlying malignancy or pre-existing co-morbidities. * Incidence of grades 3 to 4 acute GVHD occurring within 45 days of the first TAA-T infusion. * Incidence of unexpected toxicities of any grade attributed to the infusion of TAA-T occurring within 45 days of the first TAA-T dose.
Anti-tumor activity based on tumor response
Determine the number of patients who respond to TAA-T cells
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