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Varicella Zoster Virus Vaccine and GD2-T cells in Treating Participants with Refractory or Metastatic GD2 Positive Sarcomas

Trial Status: Active

This phase I trial studies the side effects and best dose of autologous iC9-GD2-CAR-expressing VZV-specific T lymphocytes (GD2-T cells) when given together with varicella-zoster virus strain Oka / Merck live antigen (varicella zoster virus vaccine), and to see how well they work in treating participants with GD2 positive sarcomas that do not respond to treatment (refractory) or have spread to other places in the body (metastatic). 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. Putting a new gene that consists of an antibody that recognizes a protein called GD2 into a participant's own T cells may make them recognize tumor cells and kill them. Giving booster vaccinations with the varicella zoster virus vaccine may stimulate the GD2-T cells and make a stronger immune response.

Inclusion Criteria

  • INCLUSION - PROCUREMENT: Diagnosis of refractory or metastatic GD2-positive sarcoma not responsive to standard treatment; (patients with osteosarcoma do not require GD2 testing of their tumor)
  • INCLUSION - PROCUREMENT: Either previously infected with varicella zoster virus (VZV; chicken pox) or previously vaccinated with VZV vaccine
  • INCLUSION - PROCUREMENT: Karnofsky/Lansky score of ≥ 50
  • INCLUSION - PROCUREMENT: Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent
  • INCLUSION - TREATMENT: Diagnosis of refractory or metastatic GD2-positive sarcoma not responsive to standard treatment; (patients with osteosarcoma do not require GD2 testing of their tumors)
  • INCLUSION - TREATMENT: Recovered from the acute toxic effects of all prior chemotherapy
  • INCLUSION - TREATMENT: Karnofsky/Lansky score of ≥ 50
  • INCLUSION - TREATMENT: Bilirubin ≤ 3x
  • INCLUSION - TREATMENT: Aspartate aminotransferase (AST) ≤ 5x
  • INCLUSION - TREATMENT: Serum creatinine ≤ 2x upper limit of normal
  • INCLUSION - TREATMENT: Hemoglobin (Hgb) ≥ 9.0 g/dl
  • INCLUSION - TREATMENT: Absolute neutrophil count (ANC) >500/ul
  • INCLUSION - TREATMENT: Platelets > 50,000/ul
  • INCLUSION - TREATMENT: Pulse oximetry of ≥ 90% on room air
  • INCLUSION - TREATMENT: Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the cytotoxic T-lymphocyte (CTL) infusion; male partner should use a condom
  • INCLUSION - TREATMENT: Available autologous transduced cytotoxic T lymphocytes with ≥ 20% expression of GD2 CAR and killing of GD2-positive targets ≥ 20% in cytotoxicity assay
  • INCLUSION - TREATMENT: Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent

Exclusion Criteria

  • EXCLUSION - PROCUREMENT: Known primary immune deficiency or human immunodeficiency virus (HIV) positivity
  • EXCLUSION - TREATMENT: Severe intercurrent infection
  • EXCLUSION - TREATMENT: Known primary immune deficiency or HIV positivity
  • EXCLUSION - TREATMENT: Pregnant or lactating
  • EXCLUSION - TREATMENT: History of hypersensitivity reactions to murine protein-containing products
  • EXCLUSION - TREATMENT: Known allergy to VZV vaccine

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Contact: Lisa Lynn Wang
Phone: 832-824-4822
Center for Cell and Gene Therapy
Status: ACTIVE
Contact: Lisa Lynn Wang
Phone: 832-824-4822
Texas Children's Hospital
Status: ACTIVE
Contact: Lisa Lynn Wang
Phone: 832-824-4822

PRIMARY OBJECTIVES:

I. To determine the safety of infusing autologous varicella zoster virus (VZV)-specific T cells engrafted with a GD2-specific chimeric antigen receptor (CAR) combined with vaccination with a commercially available VZV vaccine in patients with advanced GD2-positive sarcomas.

SECONDARY OBJECTIVES:

I. To assess the in vivo persistence of infused T cells using immunoassays and transgene detection.

II. To assess the effects of VZV vaccination on the in vivo expansion and persistence of transgenic VZV-specific T cells.

III. To assess the anti-tumor effects of the infused GD2-specific T cells.

OUTLINE: This is a dose escalation study of GD2-T cells.

Participants receive lower doses of GD2-T cells intravenously (IV) over 1-10 minutes on day 0 and VZV vaccine on day 42. Participants receiving higher doses of GD2-T cells receive VZV vaccine 48 hours prior to receiving GD2-T cells IV on day 0.

Upon completion of study treatment, participants are followed up at 3, 6, 9, 12, 15, and 18 months, every 6 months for 4 years, and then yearly for up to 15 years total.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Lisa Lynn Wang

  • Primary ID VEGAS
  • Secondary IDs NCI-2018-00702, H-32335
  • Clinicaltrials.gov ID NCT01953900