NCT02311621

Engineered Neuroblastoma Cellular Immunotherapy (ENCIT)-01

A Phase 1 Feasibility and Safety Study of Cellular Immunotherapy for Recurrent/Refractory Neuroblastoma Using Autologous T-cells Lentivirally Transduced to Express CD171-specific Chimeric Antigen Receptors

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 65 (estimated)
• Sponsor: Seattle Children's Hospital · Academic / Other
• Sex: All
• Age: 18 Months – 26 Years
• Healthy volunteers: Not accepted

Summary

Patients with recurrent or refractory neuroblastoma are resistance to conventional chemotherapy. For this reason, the investigators are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a chimeric antigen receptor (CAR). The CAR enables the T cell to recognize and kill the neuroblastoma cell through the recognition of CD171, a protein expressed of the surface of the neuroblastoma cell in patients with neuroblastoma. This is a phase 1 study designed to determine the maximum tolerated dose of the CAR+ T cells.

Detailed description

Upon meeting the eligibility requirements and enrolling on study, subjects will undergo apheresis to obtain the T cells for the generation of the CD171 CAR+ T cells. The T cells are isolated from the apheresis product, the CD4 and CD8 T cells are then selected and grown separately, transduced with a lentivirus to express the CD171 CAR as well as a truncated EGFR that has no signaling capacity (noted EGFRt) and expanded in culture over a 4-6 week period. During the process of cell generation, subjects will continue to be cared for by their primary oncologist and may undergo additional treatment directed at neuroblastoma during this time. After the CAR+ T cells have been generated, the subject undergoes a disease assessment and determination of necessary lymphodepletion therapy. A variety of lymphodepletion strategies are acceptable and determined on a case by case basis. At least 48 hours after the completion of lymphodepletion, the subject will receive and infusion of CAR+ T cells at an approximate 1:1 ratio of CD4 to CD8 CAR+ T cells. Following treatment with the CAR+ T cells, subjects will be followed intensely for 6 weeks with serial blood testing and re-evaluation of disease status with MIBG scintigraphy, tumor imaging by MRI/CT and bone marrow aspirates. After 4-6 weeks, the subjects clinical care will be resumed by their primary oncologist, and it is possible that they would receive additional chemotherapy or investigational agents. Some subjects will receive cetuximab for ablation of the genetically modified T cells. Criteria to receive cetuximab include acute toxicities that are life threatening, as well as studies indicating lymphoproliferative disorder arising from an infused genetically modified T cell. Upon completion of the study, subjects will be followed bi-annually for 5 years, and then annually for 10 additional years with either a medical history, physical exam and blood tests or a phone call/questionnaire. This follow up will help to determine if the subject develops any long-term health problems related to the CAR+ T cells including a new cancer.

Conditions

• Neuroblastoma
• Ganglioneuroblastoma

Interventions

Type	Name	Description
BIOLOGICAL	Patient Derived CD171 specific CAR T cells expressing EGFRt (2nd generation T cells)	Intravenous infusion of autologous T cells transduced to express 4-1BB:zeta CD171CAR and EGFRt (2nd generation T cells)
BIOLOGICAL	Patient Derived CD171 specific CAR T cells expressing EGFRt (3rd generation T cells)	Intravenous infusion of autologous T cells transduced to express CD28:4-1BB:zeta CD171CAR and EGFRt
BIOLOGICAL	Patient Derived CD171 specific CAR T cells expressing EGFRt (long spacer 2nd generation T cells)	Intravenous infusion of autologous T cells transduced to express 4-1BB:zeta CD171CAR and EGFRt (long spacer 2nd generation T cells)

Timeline

• Start date: 2014-11-25
• Primary completion: 2023-11-01
• Completion: 2038-11-01
• First posted: 2014-12-08
• Last updated: 2025-05-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study