iC9-GD2-CAR-VZV-CTLs/Refractory or Metastatic GD2-positive Sarcoma and Neuroblastoma

NCT01953900 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: H-32335 VEGASVEGASP01CA094237
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find the largest safe dose of GD2-T cells (also called iC9-GD2-CAR-VZV-CTLs) in combination with a varicella zoster vaccine and lymohodepleting chemotherapy. Additionally, we will learn what the side effects of this treatment are and to see whether this therapy might help patients with advanced osteosarcoma and neuroblastoma. Because there is no standard treatment for recurrent/refractory osteosarcoma and neuroblastoma at this time or because the currently used treatments do not work fully in all cases, patients are being asked to volunteer to take part in a gene transfer research study using special immune cells. 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: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. Investigators have found from previous research that a new gene can be put into T cells that will make them recognize cancer cells and kill them. Investigators now want to see if a new gene can be put in these cells that will let the T cells recognize and kill sarcoma and neuroblastoma cells. The new gene is called a chimeric antigen receptor (CAR) and consists of an antibody called 14g2a that recognizes GD2, a protein that is found on sarcoma and neuroblastoma cells (GD2-CAR). In addition, it contains parts of the CD28 and OX40 genes which can stimulate T cells to make them live longer. Investigators have found that CAR-T cells can kill some of the tumor, but they don't last very long in the body and so the tumor eventually comes back. T cells that recognize the virus that causes chicken pox, varicella zoster virus (VZV), remain in the bloodstream for many years especially if they are stimulated or boosted by the VZV vaccine. Investigators will therefore insert the GD2-CAR gene into T cells that recognize VZV. These cells are called iC9-GD2-CAR-VZV-specific T cells but are referred to as GD2-T cells for simplicity.

Conditions

Osteosarcoma; Neuroblastoma

Keywords

Osteosarcoma; T-Cells; varicella zoster virus (VZV); GD2; Neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity

  The primary objective is to evaluate the safety and feasibility of intravenous injections of autologous iC9-GD2-CAR-VZV-CTLs in combination with VZV vaccination in patients with advanced GD2-positive sarcomas or neuroblastoma.

  6-weeks

Secondary Outcomes (2)

• Amount of T cells in the blood after the infusions

  15 years

• Number of patients with a response to the T cells

  14 weeks

Study Arms (1)

GD2 T cells plus VZV vaccine

EXPERIMENTAL

In this study we will be administering from 1 x 10\^6 to 1 x 10\^9 transduced autologous VZV-specific CTLs, derived from VZV-specific memory T cells, so there will be no risk of alloreactivity. 6.1.1 Pre-infusion lymphodepletion for dose levels 9-11: Patients will receive 3 daily doses of cyclophosphamide together with fludarabine to induce lymphopenia, finishing at least 24 hours before T cell infusion. Cyclophosphamide will be given at a dose of 500 mg/m2/day followed by Fludarabine 30 mg/m2/day.

Genetic: GD2 T cells; Biological: VZV vaccine; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

GD2 T cells GENETIC

On dose levels 1 and 2 each patient receives one injection of GD2 T cells followed by VZV vaccine injection 42 days later. Dose Level 1: 1x10\^6 cells/m\^2 Dose Level 2: 1x10\^7 cells/m\^2 The next dose levels to be studied following Dose level 2 are Dose levels 7 and 8 where subjects will receive the VZV vaccine followed by a single infusion of iC9-GD2-CAR-VZV-CTLs within 48 hours after VZV vaccine: Dose Level 7: 1 x 10\^7 cells/m2 Dose Level 8: 1 x 10\^8 cells/m\^2 Dose levels 9-11 will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine prior to administration of the T cells. Dose Level 9: 1 x 10\^8 cells/m\^2 Dose Level 10: 5 x 10\^8 cells/m\^2 Dose Level 11: 1 x 10\^9 cells/m\^2 The previously planned dose levels 3-6 will not be studied.

Also known as: iC9-GD2-CAR-VZV-CTL

GD2 T cells plus VZV vaccine

VZV vaccine BIOLOGICAL

Subjects will receive a VZV vaccine with CTL infusion within 48 hours after the vaccine.

Also known as: zostavax

GD2 T cells plus VZV vaccine

Fludarabine DRUG

Pre-infusion lymphodepletion for dose levels 9-11: Patients will receive 3 daily doses of cyclophosphamide together with fludarabine to induce lymphopenia, finishing at least 24 hours before T cell infusion. Cyclophosphamide will be given at a dose of 500 mg/m\^2/day followed by Fludarabine 30 mg/m\^2/day. Infusions should be given following hospital/pharmacy recommendations however at a minimum the cyclophosphamide should be infused over 1 hour and the fludarabine should be infused over 30 minutes. Mesna, IV hydration, and anti-emetics will be provided following local institutional guidelines. T cell infusion will take place the day after completion of chemotherapy. Zostavax will be administered two weeks after infusion of T cells.

Also known as: Fludara

GD2 T cells plus VZV vaccine

Cyclophosphamide DRUG

Pre-infusion lymphodepletion for dose levels 9-11: Patients will receive 3 daily doses of cyclophosphamide together with fludarabine to induce lymphopenia, finishing at least 24 hours before T cell infusion. Cyclophosphamide will be given at a dose of 500 mg/m\^2/day followed by Fludarabine 30 mg/m\^2/day. Infusions should be given following hospital/pharmacy recommendations however at a minimum the cyclophosphamide should be infused over 1 hour and the fludarabine should be infused over 30 minutes. Mesna, IV hydration, and anti-emetics will be provided following local institutional guidelines. T cell infusion will take place the day after completion of chemotherapy. Zostavax will be administered two weeks after infusion of T cells.

Also known as: Cytoxan

GD2 T cells plus VZV vaccine

Eligibility Criteria

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

You may qualify if:

• Procurement:
• Diagnosis of relapsed or refractory osteosarcoma OR relapsed or refractory high risk neuroblastoma not responsive to standard treatment.
• Either previously infected with varicella zoster virus(VZV; chicken pox) or previously vaccinated with VZV vaccine
• Karnofsky/Lansky score of greater than or equal to 50
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
• Treatment:
• Diagnosis of relapsed or refractory osteosarcoma OR relapsed or refractory high risk neuroblastoma not responsive to standard treatment.
• Recovered from the acute toxic effects of all prior chemotherapy
• Karnofsky/Lansky score of greater than or equal to 50
• Bilirubin less than or equal to 3x upper limit of normal, AST less than or equal to 5x upper limit of normal, Serum creatinine less than or equal to 2x upper limit of normal, Hgb greater than or equal to 7.0 g/dl, ANC\>500/uL, platelets \> 50,000/uL
• Pulse oximetry of greater than or equal to 90% on room air
• Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the CTL infusion. Male partner should use a condom.
• Available autologous transduced cytotoxic T lymphocytes with greater than or equal to 20% expression of GD2 CAR and killing of GD2-positive targets greater than or equal to 20% in cytotoxicity assay
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

You may not qualify if:

• Procurement:
• Known primary immune deficiency or HIV positivity
• Treatment:
• Severe intercurrent infection
• Known primary immune deficiency or HIV positivity
• Pregnant or lactating
• History of hypersensitivity reactions to murine protein-containing products
• Known allergy to VZV vaccine

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Cancer Institute (NCI): collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

• Tanaka M, Tashiro H, Omer B, Lapteva N, Ando J, Ngo M, Mehta B, Dotti G, Kinchington PR, Leen AM, Rossig C, Rooney CM. Vaccination Targeting Native Receptors to Enhance the Function and Proliferation of Chimeric Antigen Receptor (CAR)-Modified T Cells. Clin Cancer Res. 2017 Jul 15;23(14):3499-3509. doi: 10.1158/1078-0432.CCR-16-2138. Epub 2017 Feb 9.

  PMID: 28183713 DERIVED

MeSH Terms

Conditions

Osteosarcoma; Neuroblastoma; Chickenpox

Interventions

Herpes Zoster Vaccine; fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Chickenpox Vaccine; Herpesvirus Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Lisa L Wang, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Cliona Rooney, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

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: Professor

Study Record Dates

• First Submitted: September 26, 2013
• First Posted: October 1, 2013
• Study Start: April 1, 2014
• Primary Completion: October 31, 2019
• Study Completion (Estimated): October 31, 2034
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

US (2)