Her2 Chimeric Antigen Receptor Expressing T Cells in Advanced Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Baylor College of Medicine
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Nabil Ahmed, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00902044
First received: May 13, 2009
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

Patients have a type of cancer called sarcoma. The sarcoma has come back after treatment. Because there is no standard treatment for the patients cancer 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 disease: antibodies and T cells. We hope that both will work better together. Antibodies are proteins that protect the body from diseases caused by germs or toxic substances. They work by binding those germs or substances, which stops them from growing or exerting their toxic effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers: they both have shown promise, but have not been strong enough to cure most patients.

We have found from previous research that we can put a new gene into T cells that will make them recognize cancer cells and kill them. We now want to see if we can put a new gene in these cells that will let the T cells recognize and kill sarcoma cells. The new gene that we will put in makes an antibody specific for HER2 (Human Epidermal Growth Factor Receptor 2) that binds to sarcoma cells. In addition it contains CD28, which stimulated T cells and make them last longer.

The purpose of this study is to find the largest safe dose of chimeric T cells, to learn what the side effects are, and to see whether this therapy might help patients with sarcoma.


Condition Intervention Phase
Sarcoma
Genetic: Autologous HER2-specific T cells
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Administration of Her2 Chimeric Antigen Receptor Expressing T Cells for Subjects With Advanced Sarcoma (HEROS)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Number of patients with dose limiting toxicity after one injection of HER2-specific T cells [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    To determine the safety of one intravenous injection of autologous T cells expressing HER2-specific chimeric antigen receptor (CAR) in patients with advanced HER2-positive sarcoma.


Secondary Outcome Measures:
  • Frequency of HER2-specific T cells pre and post injection [ Time Frame: 15 years ] [ Designated as safety issue: No ]
    To assess the in vivo persistence of infused T cells using immunoassays and transgene detection

  • Change in tumor size from pre to post injection [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    To assess the anti-tumor effects of the infused HER2-specific T cells


Estimated Enrollment: 36
Study Start Date: July 2009
Estimated Study Completion Date: July 2030
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Autologous HER2-specific T cells

Dose Level 1: 1x10^4 cells/m2

Dose Level 2: 3x10^4 cells/m2

Dose Level 3: 1x10^5 cells/m2 (NOT BEING USED)

Dose Level 4: 3x10^5 cells/m2 (NOT BEING USED)

Dose Level 5: 1x10^6 cells/m2

Dose Level 6: 3x10^6 cells/m2

Dose Level 7: 1x10^7 cells/m2

Dose Level 8: 3x10^7 cells/m2

Dose Level 9: 1x10^8 cells/m2

Genetic: Autologous HER2-specific T cells

Each patient will receive one intravenous injection of autologous HER2-specific T cells at one of the dose levels.

If the patient has stable disease or a reduction in the size of the tumor they can receive up to 6 additional doses of T cells.


Detailed Description:

Because the cells have a new gene in them the patient will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.

When the patient is enrolled on this study, they will be assigned a dose of HER2-CD28 T cells.

The patient will be given an injection of cells into the vein through an IV line at the assigned dose. The injection will take between 1 and 10 minutes. The patient will be followed in the clinic after the injection for 1 to 4 hours.

Each patient will be followed for 6 weeks after the T-cell infusion for evaluation of toxicity. They will have standard tests and procedures as well as research blood draws.

If the patient has stable disease (the tumor did not grow) or there is a reduction in the size of the tumor on imaging studies after the T-cell infusion, they can receive additional doses of the T cells at 6 to 12 weeks intervals.

  Eligibility

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

INCLUSION CRITERIA:

Procurement Eligibility:

  1. Diagnosis of refractory HER2-positive sarcoma or metastatic HER2-positive osteosarcoma, not treatable by surgical resection.
  2. Karnofsky/Lansky score of 50 or greater
  3. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

Treatment Eligibility:

  1. Diagnosis of refractory HER2-positive sarcoma or metastatic HER2-positive sarcoma, not treatable by surgical resection and with disease progression after receiving at least one prior systemic therapy.
  2. Recovered from the acute toxic effects of all prior chemotherapy at least 4 weeks before entering this study.
  3. Normal ECHO (Left ventricular ejection fraction (LVEF) has to be with in normal, institutional limits)
  4. Life expectancy 6 weeks or greater
  5. Karnofsky/Lansky score of 50 or greater
  6. Bilirubin 3x or less, AST 5x or less, Serum creatinine 2x upper limit of normal or less, Hgb 9.0 g/dl or greater, WBC greater than 2,000/ul, ANC greater than 1,000/ul, platelets greater than 100,000/ul
  7. Pulse oximetry of 90% or greater on room air
  8. 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
  9. Available autologous transduced T lymphocytes with 15% or more expression of HER2 CAR as determined by flow-cytometry and killing of HER2-positive targets 20 % or greater in cytotoxicity assay.
  10. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

EXCLUSION CRITERIA:

At time of Procurement:

1. Known HIV positivity

At time of Treatment:

  1. Severe intercurrent infection
  2. Known HIV positivity
  3. Pregnant or lactating
  4. History of hypersensitivity reactions to murine protein-containing products
  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: NCT00902044

Contacts
Contact: Nabil M Ahmed, MD 834-824-4611 nmahmed@txch.org
Contact: Catherine Perera 832-824-4594 csperera@txch.org

Locations
United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Nabil M Ahmed, MD    832-824-4611    nmahmed@txch.org   
Contact: Stephen S Gottschalk    832-824-4719    smgottsc@txch.org   
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Nabil M Ahmed, MD    832-824-4611    nmamed@txch.org   
Contact: Stephen Gottschalk, MD    832-824-4179    smgottsc@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Principal Investigator: Nabil M Ahmed, MD Baylor College of Medicine/Texas Children's Hospital
  More Information

No publications provided

Responsible Party: Nabil Ahmed, Assistant Professor, Pediatric Hematology Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00902044     History of Changes
Other Study ID Numbers: 24489-HEROS, HEROS
Study First Received: May 13, 2009
Last Updated: August 22, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Refractory Sarcoma
Metastatic Sarcoma
Sarcoma
HER2-positive
Gene Therapy
HER2-specific T cells

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

ClinicalTrials.gov processed this record on October 29, 2014