This is an open-label 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 following lymphodepleting conditioning with or without local tumor ablation for pediatric and adult patients with high-risk solid tumors due to the presence of refractory, relapsed and/or minimal residual detectable disease following conventional therapy (e.g., 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Diagnosis of high-risk solid tumors known to express at least 2 targeted antigens by either histology or historical reference: Ewing sarcoma, Wilms tumor, neuroblastoma, rhabdomyosarcoma, soft tissue sarcoma, and osteosarcoma.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.
Following conventional therapy: refractory disease, residual detectable disease, or relapsed disease.
Age >= 1 year and <70 years
Patients with uncontrolled infections. Uncontrolled infections are defined as bacterial, fungal, or viral infections with either clinical signs of worsening despite standard therapy. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to protocol treatment.
For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to initiating protocol treatment.
Patients who received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days prior to initiating protocol treatment.
Sequential
Tumor-associated antigen-specific T cell (TAA-T)
Biological/VaccinePatients will receive cells due to the presence of refractory disease, or high risk for disease relapse and/or minimal residual detectable disease following conventional therapy. The treatment schedule is as follows: Patients will receive an infusion of partially HLA-matched TAA-T any time \>1 week after completing most recent course of conventional (noninvestigational) therapy for their disease. For patients enrolled to DL2 or DL3, they will receive protocol-described lymphodepletion (LD) chemotherapy (fludarabine and cyclophosphamide) \>2 weeks from most recent course of conventional therapy and post nadir and recovery from the prior therapy. Patients will be enrolled to one of the following TAA-T dose levels: BSA \<1.20 Dose Level 2 (+/- ablation + low dose TAA-T cells) 2x10\^7 Dose Level 3 (+/- ablation + high dose TAA-T cells) 4x10\^7 BSA\>=1.20 Dose Level 2 (+/- ablation + low dose TAA-T cells) 4x10\^7 Dose Level 3 (+/- ablation + high dose TAA-T cells) 8x10\^7
To determine the safety of administering partially HLA-matched TAA-T cells
Safety will be evaluated by the incidence of dose-limiting toxicities (DLTs).
Treatment feasibility and impact of TAA-T infusion
Determining anti-tumor activity (tumor response) following TAA-T infusion.
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