HER2-Specific T Cells in Treating Patients With HER2-Positive Refractory or Metastatic Sarcoma

Status: Active

Description

The purpose of this study is to obtain blood from sarcoma patients to see if researchers can make cells that are able to fight and kill sarcoma cells. If researchers are able to do this, these T cells may be offered back to the patient in the future if the patient is eligible to participate in a treatment research study using these cells. Should this occur, as separate consent will be obtained that will provide much more information about the risks and potential benefits of this treatment. The purpose of this study is also 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.

Eligibility Criteria

Inclusion Criteria

  • PROCUREMENT ELIGIBILITY:
  • Diagnosis of refractory HER2-positive sarcoma or metastatic HER2-positive sarcoma, not treatable by surgical resection
  • Karnofsky/Lansky score of >= 50
  • Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent
  • TREATMENT ELIGIBILITY:
  • 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
  • Recovered from the acute toxic effects of all prior chemotherapy at least 4 weeks before entering this study
  • Normal echocardiogram (ECHO) (Left ventricular ejection fraction [LVEF] has to be within normal, institutional limits)
  • Life expectancy >= 6 weeks
  • Karnofsky/Lansky score of >= 50
  • Bilirubin =< 3 x upper limit of normal
  • Aspartate aminotransferase (AST) =< 5 x upper limit of normal
  • Serum creatinine =< 2 x upper limit of normal
  • Hemoglobin (Hgb) >= 9.0 g/dl
  • White blood cell (WBC) >= 2,000/ul
  • Absolute neutrophil count (ANC) >= 1,000/ul
  • Platelets > 100,000/ul
  • Pulse oximetry of >= 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 cytotoxic T lymphocyte (CTL) infusion; male partner should use a condom
  • Available autologous transduced cytotoxic T lymphocytes with >= 15% expression of HER2 CAR and killing of HER2-positive targets >= 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 ELIGIBILITY:
  • Known human immunodeficiency virus (HIV) positivity
  • TREATMENT ELIGIBILITY:
  • Severe intercurrent infection
  • Known HIV positivity
  • Pregnant or lactating
  • History of hypersensitivity reactions to murine protein-containing products

Locations & Contacts

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Nabil Ahmed
Phone: 713-798-1354
Email: burton@bcm.edu
Center for Cell and Gene Therapy
Status: Active
Contact: Nabil Ahmed
Email: burton@bcm.edu
Texas Children's Hospital
Status: Active
Contact: Nabil Ahmed
Email: burton@bcm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the safety of one intravenous injection of autologous T cells expressing human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) in patients with advanced HER2-positive sarcoma.

SECONDARY OBJECTIVES:

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

II. To assess the anti-tumor effects of the infused HER2-specific T cells.

OUTLINE: This is a dose-escalation study.

Patients receive ex vivo-expanded HER2-specific T cells intravenously (IV) over 1-10 minutes. Patients achieving stable disease or a response at their 6 week or subsequent evaluations are eligible to receive up to 6 additional doses of ex vivo-expanded HER2-specific T cells at 6 to 12 weeks intervals.

After completion of study treatment, patients are followed up 2, 4 and 6 weeks, and then every three months for a year, every 6 months for 4 years, and then annually for 10 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

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

Principal Investigator
Nabil Ahmed

Trial IDs

Primary ID HEROS
Secondary IDs NCI-2012-00634, H-24489
Clinicaltrials.gov ID NCT00902044