This is a phase I dose-escalation study to determine the safety and feasibility of autologous CAR-TA T cells (B7-H3 CAR+ T cells administered with DNR-PRAME Tumor Antigen-specific T cells) following lymphodepleting chemotherapy in participants with relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma and Wilms tumor.
Patients will be enrolled to one of three planned dose levels with B7-H3 CAR T cell dose determined based on the percentage of B7-H3 transduced cells (B7-H3+ population of cells), and dTBRII-transduced PRAME TA-specific T cell dose based on the total cell population. Both doses will be based on the recipient's body weight.
The safety of the CAR-TA T cell product will be evaluated and the maximum tolerated dose (MTD) will be determined. The safety endpoint will be assessed by monitoring for dose limiting toxicities for 28 days following CAR-TA T cell administration.
Diagnosis of relapsed/refractory rhabdomyosarcoma, Ewing sarcoma, neuroblastoma, or Wilms tumor
Refractory disease, residual detectable disease or relapsed disease following available standard of care therapies with known clinical benefit for their specific tumor type, or unable to receive such therapies due to unacceptable toxicity or contraindication
Measurable or evaluable disease by imaging, as determined following most recent therapy
Age ≥ 1 year and < 24 years
Patients with known CNS disease.
Patients with uncontrolled infection/s or known HIV infection
Pregnant or lactating females.
Patients who have undergone previous allogeneic stem cell transplant.
Children's National Research Institute
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Cancer Research UK
Collaborator
The Mark Foundation for Cancer Research
Collaborator