Engineered Neuroblastoma Cellular Immunotherapy (ENCIT)-01

NCT02311621 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ENCIT-01
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Neuroblastoma; Ganglioneuroblastoma

Keywords

CAR T cell; pediatric; young adults

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity

  Patients will be evaluated through day 28 for occurrence of dose limiting toxicity

  28 days

Secondary Outcomes (1)

• Response (Tumor response will be evaluated by the revised International Neuroblastoma Response Criteria)

  42 days

Study Arms (3)

A: 2nd Generation CE7R CAR T Cells

EXPERIMENTAL

Autologous CD4 and CD8 cells are lentivirally transduced to generate patient-derived CD171 specific CAR T cells also expressing an EGFRt. Patients will receive lymphodepletion chemotherapy prior to T cell infusion. CD171 specific CAR T cells will be administered approximately 2-3 days after lymphodepletion chemotherapy. Cells will be administered approximately 1:1 CD4 and CD8 cells with planned dose level evaluations of total T cell dose of 1x10\^6 cells/kg, 5x10\^6 cells/kg, 1x10\^7 cells/kg, 5x10\^7 cells/kg, and 1x10\^8 cells/kg will be evaluated.

Biological: Patient Derived CD171 specific CAR T cells expressing EGFRt (2nd generation T cells)

B: 3rd Generation CE7R CAR T Cells

EXPERIMENTAL

Autologous CD4 and CD8 cells are lentivirally transduced to generate patient-derived CD171 specific CAR T cells also expressing an EGFRt. Patients will receive lymphodepletion chemotherapy prior to T cell infusion. CD171 specific CAR T cells will be administered approximately 2-3 days after lymphodepletion chemotherapy. Cells will be administered approximately 1:1 CD4 and CD8 cells with planned dose level evaluations of total T cell dose of 1x10\^6 cells/kg, 5x10\^6 cells/kg, 1x10\^7 cells/kg, 5x10\^7 cells/kg, and 1x10\^8 cells/kg will be evaluated.

Biological: Patient Derived CD171 specific CAR T cells expressing EGFRt (3rd generation T cells)

C: Long Spacer 2nd Generation CE7R CAR T Cells

EXPERIMENTAL

Autologous CD4 and CD8 cells are lentivirally transduced to generate patient-derived CD171 specific CAR T cells also expressing an EGFRt. Patients will receive lymphodepletion chemotherapy prior to T cell infusion. CD171 specific CAR T cells will be administered approximately 2-3 days after lymphodepletion chemotherapy. Cells will be administered approximately 1:1 CD4 and CD8 cells with planned dose level evaluations of total T cell dose of 1x10\^6 cells/kg, 5x10\^6 cells/kg, 1x10\^7 cells/kg, 5x10\^7 cells/kg, and 1x10\^8 cells/kg will be evaluated.

Biological: Patient Derived CD171 specific CAR T cells expressing EGFRt (long spacer 2nd generation T cells)

Interventions

Patient Derived CD171 specific CAR T cells expressing EGFRt (2nd generation T cells) BIOLOGICAL

Intravenous infusion of autologous T cells transduced to express 4-1BB:zeta CD171CAR and EGFRt (2nd generation T cells)

A: 2nd Generation CE7R CAR T Cells

Patient Derived CD171 specific CAR T cells expressing EGFRt (3rd generation T cells) BIOLOGICAL

Intravenous infusion of autologous T cells transduced to express CD28:4-1BB:zeta CD171CAR and EGFRt

B: 3rd Generation CE7R CAR T Cells

Patient Derived CD171 specific CAR T cells expressing EGFRt (long spacer 2nd generation T cells) BIOLOGICAL

Intravenous infusion of autologous T cells transduced to express 4-1BB:zeta CD171CAR and EGFRt (long spacer 2nd generation T cells)

C: Long Spacer 2nd Generation CE7R CAR T Cells

Eligibility Criteria

• Age: 18 Months - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Prior diagnosis of NB or ganglioneuroblastoma either by histologic verification and/or demonstration of tumor cells in the bone marrow with increased catecholamine levels.
• Male or female subjects ≤ 26 years of age
• Diagnosis of high risk NB at initial diagnosis or if non-high risk at time of initial diagnosis must have had evidence of metastatic progression when \> 18 months of age.
• Measurable or evaluable disease
• Lansky or Karnofsky performance status score of ≥ 50
• Life expectancy of ≥ 8 weeks.
• Recovered from significant acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment onto this study.
• ≥ 7 days since last chemotherapy or biologic therapy administration
• No systemic corticosteroids (unless physiologic replacement dosing) within 7 days of enrollment. Topical Administration (e.g. inhaled or dermatologic) is allowed.
• ≥ 3 half-lives or 30 days from time of last dose of anti-tumor directed antibody therapy, whichever is shorter from time of enrollment
• ≥ 6 weeks from myeloablative therapy and autologous stem cell transplant (timed from stem cell infusion). Patients who received stem cell infusion following non-myelo-ablative therapy are eligible once they meet all other eligibility requirements. Patient must NOT have received a prior allogeneic hematopoietic stem cell transplant.
• No prior genetically modified cell therapy that is still detectable.
• Must not be receiving external beam radiation therapy at the time of study enrollment. ≥ 12 weeks from prior I131 MIBG therapy.
• Adequate organ function
• Adequate laboratory values

You may not qualify if:

• History of relevant CNS pathology or current relevant CNS pathology (non-febrile seizure disorder requiring ongoing anti-epileptic medications, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder). Patients may have CNS intracranial tumor.
• Pregnant or breast-feeding
• Unable to tolerate apheresis procedure including placement of temporary apheresis catheter if necessary
• Presence of active malignancy other than NB
• Presence of known intracranial metastatic neuroblastoma. Skull based disease with soft tissue extension is allowed.
• Presence of active severe infection
• Presence of any concurrent medical condition that, in the opinion of the protocol PI or designee, would prevent the patient from undergoing protocol-based therapy.
• Presence of a primary immunodeficiency/bone marrow failure syndrome
• Receiving any other anti-cancer agents or radiotherapy at the time of study entry
• Unwilling or unable to provide consent/assent for participation in the study and 15-year follow-up

Sponsors & Collaborators

• Seattle Children's Hospital: lead
• The Evan Foundation: collaborator
• Ben Towne Center for Childhood Cancer Research: collaborator

Study Sites (1)

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Ganglioneuroblastoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Catherine Albert, MD

  Seattle Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Seattle Children's Therapeutics

Study Record Dates

• First Submitted: December 4, 2014
• First Posted: December 8, 2014
• Study Start: November 25, 2014
• Primary Completion: November 1, 2023
• Study Completion (Estimated): November 1, 2038
• Last Updated: May 28, 2025

Record last verified: 2025-05

Locations

US (1)