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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Baylor College of Medicine
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Texas Children's Hospital
Information provided by (Responsible Party):
Lisa Wang, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01953900
First received: September 26, 2013
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

PLEASE NOTE - THIS STUDY IS CURRENTLY ONLY RECRUITING PARTICIPANTS WITH OSTEOSARCOMA.

The purpose of this study is to find the largest safe dose of GD2-T cells (also called iC9-GD2-CAR-VZV-CTLs), and additionally to evaluate if a VZV vaccine can improve the expansion and persistence of infused T cells, to learn what the side effects are, and to see whether this therapy might help patients with advanced sarcomas. Because there is no standard treatment for recurrent/refractory sarcomas 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 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 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.

This study consists of two groups. The first group of patients will receive GD2-T cells followed six weeks later by vaccination with the VZV vaccine. The second group will receive GD2-T cells, the vaccine, and a second dose of GD2-T cells two days after the vaccine. We want to see whether giving a second dose of GD2-T cells right after the vaccine helps them to be more effective.


Condition Intervention Phase
Sarcomas
Genetic: GD2 T cells
Biological: VZV vaccine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vaccination to Enhance the Anti-Tumor Activity of GD2 Chimeric Antigen Receptor-Expressing, VZV-Specific T Cells in Subjects With Advanced Sarcomas (VEGAS)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Number of subjects with a dose limiting toxicity [ Time Frame: 6-weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of patients with a response to the T cells [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]

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

    Evaluations of tumor size will be performed within 4 weeks of beginning treatment and 6 weeks (before the vaccine) and 12 to 14 weeks after the iC9-GD2-CAR-VZV-CTL injection. All patients who receive the first infusion will be evaluable for response.


  • Amount of T cells in the blood after the infusions [ Time Frame: 15 years ] [ Designated as safety issue: No ]

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

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



Estimated Enrollment: 26
Study Start Date: April 2014
Estimated Study Completion Date: April 2033
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GD2 T cells plus VZV vaccine Genetic: GD2 T cells

Each patient will receive one injection of GD2 T cells followed by VZV vaccine injection 42 days later.

The first 3 dose levels to be evaluated are:

Dose Level 1: 1x10^6 cells/m2

Dose Level 2: 1x10^7 cells/m2

Dose Level 3: 1x10^8 cells/m2

If dose levels 1 through 3 prove to be safe, the next subjects enrolled will receive one injection of the GD2 T cells followed by the VZV vaccine 42 days later and then they will receive a second dose of GD2 T cells 2 days after the vaccine. The first injection of GD2 T cells will be 1 x 10^8 cells/m2. The second injection dose level will be as follows:

Dose Level 4: 1 x 10^6 cells/m2

Dose Level 5: 1 x 10^7 cells/m2

Dose Level 6: 1 x 10^8 cells/m2

Other Name: iC9-GD2-CAR-VZV-CTL
Biological: VZV vaccine
All subjects will receive a dose of VZV vaccine 42 days after the GD2 T cells.
Other Name: varivax

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Procurement:

  • Diagnosis of refractory or metastatic GD2-positive sarcoma 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 refractory or metastatic GD2-positive sarcoma not responsive to standard treatment
  • VZV seropositive
  • Recovered from the acute toxic effects of all prior chemotherapy (at least 4 weeks from start of last chemotherapy) before entering this study
  • 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 9.0 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 determined by flow-cytometry 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

Exclusion Criteria:

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01953900

Contacts
Contact: Lisa L Wang, MD 832-824-4822 llwang@texaschildrens.org

Locations
United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Lisa L Wang, MD    832-824-4822    llwang@texaschildrens.org   
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Lisa L Wang, MD    832-824-4822    llwang@texaschildrens.org   
Principal Investigator: Lisa L Wang, MD         
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Texas Children's Hospital
Investigators
Principal Investigator: Lisa L Wang, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Lisa Wang, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01953900     History of Changes
Other Study ID Numbers: H-32335 VEGAS, VEGAS
Study First Received: September 26, 2013
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Sarcoma
T-Cells
varicella zoster virus (VZV)
GD2

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on August 18, 2014