PHOX2B PC-CAR T Cells for Relapsed Neuroblastoma

NCT07007117 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 25-02315525CT012
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first in human dose escalation trial to determine the safety of administering PHOX2B PC-CAR T cells in patients with advanced, high-risk neuroblastoma.

Conditions

Refractory Neuroblastoma; Relapsed Neuroblastoma; High-Risk Neuroblastoma

Keywords

Neuroblastoma; PHOX2B PC-CAR T Cells; Cell Therapy

Outcome Measures

Primary Outcomes (2)

• Determine the Maximum Tolerated Dose of PHOX2B PC-CAR T Cells

  The Maximum Tolerated Dose of PHOX2B-PC CAR T cells will be determined by measuring the incidence of dose limiting toxicities following administration of the product.

  5 years

• Frequency of Adverse Events Following PHOX2B PC-CAR T cell administration

  Assess the frequency and severity of treatment related adverse events following administration of PHOX2B PC-CAR T cells.

  5 years

Secondary Outcomes (4)

• Manufacturing Feasibility of PHOX2B PC-CAR T cells

  5 years

• Persistence of PHOX2B PC-CAR T cells

  5 years

• Preliminarily define the clinical activity of PHOX2B PC-CAR T cells in patients with relapsed or refractory neuroblastoma

  5 years

• Severity of Adverse Events Following Repeated dosing of PHOX2B PC-CAR T Cells

  5 years

Study Arms (2)

Dose Escalation

EXPERIMENTAL

The dose escalation arm will determine the maximum tolerated dose of PHOX2B PC-CAR T cells using a standard 3+3 trial design.

Biological: PHOX2B PC-CAR T Cells

Dose Expansion

EXPERIMENTAL

If at least one dose from the dose expansion arm is determined to be safe, additional patients will be enrolled to the dose expansion arm to preliminarily evaluate the rate of response to PHOX2B-PC CAR T cells and further characterize the safety profile of PHOX2B-PC CAR T Cells

Biological: PHOX2B PC-CAR T Cells

Interventions

PHOX2B PC-CAR T Cells BIOLOGICAL

The PHOX2B PC-CAR T cell investigational product is comprised of autologous human T cells that have been genetically modified to express a a PHOX2B-targeting chimeric antigen receptor (CAR) transgene.

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be ≥ 1 years of age
• Patients must demonstrate expression of at least one of the following HLA alleles by HLA genotyping (conducted at CHOP) to be eligible:
• HLA-A\*24:02, HLA-A\*24:03, HLA-A\*24:04, HLA-A\*24:07, HLA-A\*24:124, HLA-A\*24:143, HLA-A\*24:17, HLA-A\*24:242, HLA-A\*24:305, HLA-A\*24:314, HLA-A\*24:33, HLA-A\*24:353, HLA-A\*24:41, HLA-A\*24:51, HLA-A\*24:63, HLA-A\*24:87, HLA-A\*24:92, HLA-A\*23:01, HLA-A\*23:17, HLA-A\*23:25, HLA-A\*23:39,
• Disease Status A. Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low- or intermediate-risk, but then reclassified as high-risk are also eligible.
• B. Patients must have a previously histologically confirmed diagnosis of neuroblastoma.
• C. Patients must have recurrent/progressive, refractory or persistent neuroblastoma.
• D. Patients must have neuroblastoma for which standard curative measures do not exist or are no longer effective. Note: Patients at first relapse are eligible as no known curative therapies exist for relapsed high-risk neuroblastoma.
• E. Patients must have evaluable or measurable disease at enrollment and at least one of the following:
• Bone Sites
• a) MIBG avid tumors:
• Patients with recurrent/progressive or refractory disease:
• a. At least 1 MIBG avid bone site.
• Patients with persistent disease:
• or more MIBG avid sites (including soft tissue and/or bone).
• or 2 MIBG avid sites (including soft tissue and/or bone) with biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment.

You may not qualify if:

• Patients with active hepatitis B or active hepatitis C.
• Patients with active HIV infection (patients undergoing anti-retroviral therapy with undetectable HIV viral load are eligible).
• Patients with uncontrolled active infection.
• Patients with primary or acquired immunodeficiency disorder.
• Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
• Patients with actively progressing CNS metastases, including parenchymal or leptomeningeal involvement. (Note: CNS imaging at screening is only required if there is a clinical indication of suspected CNS metastasis)
• Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and/or neurotoxicity.
• Patients who have received any live vaccines within 30 days prior to enrollment.
• Pregnant or nursing (lactating) patients.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: collaborator
• Alliance for Cancer Gene Therapy: collaborator
• Children's Cancer Research Fund: collaborator
• Stephan Grupp MD PhD: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Neuroblastoma

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

• Jacquelyn Crane, MD

  Children's Hospital of Philadelphia

  STUDY DIRECTOR

• Stephan A. Grupp, MD, PhD

  Children's Hospital of Philadelphia

  STUDY DIRECTOR

Central Study Contacts

Melissa Varghese, B.A.

CONTACT

845-553-5358; varghesem@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Cell Therapy and Transplant Section Director, Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy Medical Director, Cell and Gene Therapy Lab at Children's Hospital of Philadelphia

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: June 5, 2025
• Study Start: June 20, 2025
• Primary Completion (Estimated): June 30, 2032
• Study Completion (Estimated): June 30, 2035
• Last Updated: December 26, 2025

Record last verified: 2025-12

Locations

US (1)