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Trial record 42 of 256 for:    "methodist hospital" | Recruiting, Not yet recruiting, Available Studies | Houston

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

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ClinicalTrials.gov Identifier: NCT01953900
Recruitment Status : Recruiting
First Posted : October 1, 2013
Last Update Posted : March 6, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Texas Children's Hospital
Information provided by (Responsible Party):
Sarah Whittle, Baylor College of Medicine

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.


Condition or disease Intervention/treatment Phase
Osteosarcoma Neuroblastoma Genetic: GD2 T cells Biological: VZV vaccine Drug: Fludarabine Drug: Cyclophosphamide Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (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 and Neuroblastoma (VEGAS)
Study Start Date : April 2014
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2036


Arm Intervention/treatment
Experimental: GD2 T cells plus VZV vaccine
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

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.

Other Name: iC9-GD2-CAR-VZV-CTL

Biological: VZV vaccine
Subjects will receive a VZV vaccine with CTL infusion within 48 hours after the vaccine.
Other Name: zostavax

Drug: Fludarabine
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.
Other Name: Fludara

Drug: Cyclophosphamide
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.
Other Name: Cytoxan




Primary Outcome Measures :
  1. Number of patients with dose limiting toxicity [ Time Frame: 6-weeks ]
    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.


Secondary Outcome Measures :
  1. Amount of T cells in the blood after the infusions [ Time Frame: 15 years ]

    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


  2. Number of patients with a response to the T cells [ Time Frame: 14 weeks ]

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

    To assess the effect of of myeloid derived suppressor cells (MDSC) on expansion and persistence of infused 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.




Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01953900


Contacts
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Contact: Sarah Whittle, MD 832-824-1471 sbwhittl@txch.org
Contact: Lisa L Wang 832-824-4822 llwang@txch.org

Locations
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United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Lisa L Wang, MD    832-824-4822    llwang@texaschildrens.org   
Contact: Jacqueline Castello    832-824-4391    jxcastel@texaschildrens.org   
Principal Investigator: Lisa L Wang, MD         
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Sarah Whittle, MD    832-824-1471    sbwhittl@txch.org   
Contact: Jacqueline Castello    832-824-4391    jxcastel@texaschildrens.org   
Principal Investigator: Sara Whittle, MD         
Sponsors and Collaborators
Baylor College of Medicine
National Cancer Institute (NCI)
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Texas Children's Hospital
Investigators
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Principal Investigator: Lisa L Wang, MD Baylor College of Medicine
Principal Investigator: Sarah Whittle, MD Pediatrics, Baylor College of Medicine
Principal Investigator: Cliona Rooney, PhD Baylor College of Medicine

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sarah Whittle, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01953900     History of Changes
Other Study ID Numbers: H-32335 VEGAS
VEGAS ( Other Identifier: CAGT )
P01CA094237 ( U.S. NIH Grant/Contract )
First Posted: October 1, 2013    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019

Keywords provided by Sarah Whittle, Baylor College of Medicine:
Osteosarcoma
T-Cells
varicella zoster virus (VZV)
GD2
Neuroblastoma

Additional relevant MeSH terms:
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Sarcoma
Neuroblastoma
Osteosarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Vaccines
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Vidarabine
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic