NKG2D.Zeta-NK Cell Conditioning With C7R.GD2.CAR-T Cells for Patients With Relapsed or Refractory Osteosarcoma or Neuroblastoma

NCT07211737 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-55743 INCITE-ON
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find the largest safe dose of i15.NKG2D.zeta-NK cells in combination with C7R.GD2.CAR-T cells, and additionally to evaluate how long they can be detected in patients' blood and what affect they have on patients' cancer. Patients eligible for this study have neuroblastoma or osteosarcoma that expresses a substance on the cancer cells called GD2. This cancer has either come back after treatment or did not respond to the standard or other investigational treatments or therapies used to treat it. There is no standard treatment for these types of advanced cancers at this time. This is a gene transfer research study using special immune cells called NK cells and T cells. NK cells and T cells are types of white blood cell that help the body fight infection. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: NK cells and T cells. T cells are special infection-fighting blood cells that can kill cells infected with viruses and tumor cells. NK cells, another kind of infection-fighting cell, can recognize a wide range of cells in distress, including tumor cells and cells that help protect tumor cells in the cancer environment. Both NK cells and T cells have been used individually to treat patients with cancers. They have shown promise, but have not been strong enough individually to cure most patients. Investigators have found from previous research that we can put a new gene into T cells that will make them recognize GD2, a substance found on almost all neuroblastoma and osteosarcoma cells. We can also put a new gene into NK cells that help them fight the tumor environment. Investigators know that T cells and NK cells need substances called cytokines to survive but the cells do not get enough cytokines after infusion into the body; therefore, the investigators have added the genes C7R and IL15 into the T and NK cells, respectively, to give each cell a constant supply of cytokine that helps them to survive longer. The C7R.GD2.CAR-T cells and i15.NKG2D.zeta-NK cells are investigational products not approved by the Food and Drug Administration.

Conditions

Relapsed Neuroblastoma; Refractory Neuroblastoma; Relapsed Osteosarcoma; Refractory Osteosarcoma

Keywords

Gene Therapy; CAR T cells; Neuroblastoma; Osteosarcoma; Immunotherapy; chimeric antigen receptor; NK Cell

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT) rate

  Proportion of participants with DLTs related to the combination of NK cell and T cell infusions evaluated as per the NCI CTCAE v5.0 criteria

  4 weeks post-CAR-T cell infusion

• Maximum tolerated dose (MTD) of i15.NKG2D.zeta-NK cells when given in combination with C7R.GD2.CAR-T cells

  The dose level of infused NK cells for which the DLT rate is approximately 0.3

  4 weeks post CAR-T infusion of the last participant

Secondary Outcomes (2)

• Objective response rate (ORR)

  6 weeks after CAR-T infusion

• Cytokine release syndrome (CRS) grade

  4 weeks post CAR-T infusion

Study Arms (1)

i15.NKG2D.zeta NK cells and C7R.GD2.CARTs cells

EXPERIMENTAL

Three dose levels will be evaluated. This is a dose escalating trial which will infuse doses of i15.NKG2D.zeta NK cells followed by a fixed dose of C7R.GD2.CAR T cells 5 days later.

Genetic: i15.NKG2D.zeta NK cells and C7R.GD2.CARTs cells

Interventions

i15.NKG2D.zeta NK cells and C7R.GD2.CARTs cells GENETIC

Dose Level 1: 3 x 10\^8/m\^2 of i15.NKG2D.zeta NK cells and 3 x 10\^7/m\^2 of C7R.GD2.CAR T cells given 5 days later.

i15.NKG2D.zeta NK cells and C7R.GD2.CARTs cells

Eligibility Criteria

• Age: 1 Year - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with Neuroblastoma that have persistent disease after standard treatment or have relapsed/refractory disease.
• Patients with Osteosarcoma that have persistent disease after standard treatment or have relapsed/refractory disease.
• Karnofsky/Lansky score of 60% or greater.
• Informed consent and assent (as applicable) obtained from parent/guardian and child.
• Greater than 1 year of age.

You may not qualify if:

• History of hypersensitivity to murine protein-containing products.
• Known presence of Human Anti-Mouse Antibodies (HAMA).
• Active autoimmune disease (requiring immunosuppressive treatment in the past 6 months).
• Primary brain tumor or known brain metastases (on evaluation by MIBG and/or PET if applicable, CT/MRI/LP not required).
• Patients with Neuroblastoma that have persistent disease after standard treatment or have relapsed/refractory disease.
• Patients with Osteosarcoma that have persistent disease after standard treatment or have relapsed/refractory disease.
• Karnofsky/Lansky score of 50% or greater
• Pulse Ox greater than or equal to 90% on room air
• AST less than 5 times upper limit of normal (less than 10 times upper normal if known with metastatic liver disease)
• Total bilirubin less than 3 times the upper limit of normal
• Serum creatinine less than 3 times upper limit of normal
• Available autologous T-cells with greater than or equal to 20% expressing GD2.CAR
• Informed consent and assent (as applicable) obtained from parent/guardian and child.
• Greater than 1 year of age.
• Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Osteosarcoma

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; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Study Officials

• Leander D Timothy, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Shoba A Navai, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Stephanie L Fetzko, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robin Parihar, MD, PhD

CONTACT

832-824-4746; rxpariha@texaschildrens.org

Martha Arredondo

CONTACT

832-824-1201; Martha.Arredondo@bcm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 4, 2025
• First Posted: October 8, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2044
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

US (1)