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Title
A Phase I Study of Infusion of HER-2/neu (HER2) Specific T Cells in Patients with Advanced Stage HER-2/neu Expressing Cancers who have Received a HER-2/neu Vaccine
 
Study Design
This is a phase I non-randomized, 2-arm study designed to evaluate the feasibility of expanding HER2-specific T cells ex vivo and to evaluate the safety of administering to patients escalating doses of ex vivo expanded HER2-specific T cells with and without post-infusion IL-2.
 
Study Contact
Nicole Bates | 206.543.6620 | E-Mail
 
Rationale
Adoptive immunotherapy has evolved from the preclinical model to a potentially feasible treatment strategy for advanced disease. We now know that antigen-specific T cell clones and lines can be safely infused into patients, that CD4 help is essential for the sustainability in vivo of the effector cells, that IL-2 plays a significant role in sustaining and promoting T cell expansion in vivo, and that lymphodepletion prior to cellular infusion may be necessary to promote post-infusion homeostatic T cell expansion. Our group has found that vaccination of patients against the HER2 oncogenic protein results in increased precursor frequencies of tumor antigen-specific T cells in vivo and ex vivo expansion of those cells from patient PBMC is markedly facilitated post-vaccination. This is a Phase I trial of adoptive immunotherapy with ex vivo expanded T cells line specific for HER2 epitopes. The target population is patients with HER2-overexpressing cancers who have progressive disease after vaccination with a HER2 vaccine. Patients will be pre-treated with cyclophosphamide. Because the cytokine milieu of the T cell lines may, when given with IL-2, result in increased side effects, we will have two patient cohorts: one that receives cellular infusions alone and one that receives cellular infusions with low-dose post infusion IL-2.
 
Study Population / Indication
Patients with progressive HER2-overexpressing metastatic breast, ovarian, or non-small cell lung cancer not considered curable by conventional therapies, including Herceptin. Patients must have measurable disease. Patients must be pre-immunized via a HER2-specific vaccination through a vaccine protocol approved through the University of Washington Human Subjects Division.
 
Number of Patients: This study will accrue a maximum of 10 patients.
 
Start Date: June 2003
 
Study Location: University of Washington Medical Center | 1959 NE Pacific Street | Seattle, WA 98195
 
Current Enrollment: 50%
 
Objectives
Primary:
  1. To assess the feasibility of expanding HER2-specific T cells ex vivo for infusion into subjects who have advanced HER2-overexpressing cancer.
  2. To assess the toxicity associated with infusing HER2-specific T cells into patients using ex vivo expanded autologous T cells with and without post-infusion low dose IL-2.
Secondary:
  1. To investigate to what extent HER2-specific T cell immunity can be boosted or generated in individuals after infusion of HER2-specific T cells.
  2. To investigate the potential anti-tumor effects of HER2-specific T cells in patients with advanced-stage cancers overexpressing the HER2 protein.
  3. To evaluate how long T cell immune augmentation persists in vivo after adoptive transfer of HER2 specific T cells with or without IL-2.
Outcome Measures
Primary endpoints:
  1. The ability to expand HER2-specific T cells derived from patients with advanced HER2-expressing cancer will be defined as feasible if the target expansion of 2x1010 HER2-specific T cells is achieved in 4/5 subjects within a group. A specific dose of HER2-specific T cells will be defined as safe if 4 of 5 subjects in a group tolerate that dose without dose-limiting toxicity (DLT). Each Arm of the study will be evaluated separately.
Secondary endpoints:
  1. The extent to which HER2-specific T cell immunity can be boosted successfully with adoptive immunotherapy will be defined by post-infusion quantitative assessment of HER2-specific CD4+ or CD8+ precursors assessed by cytokine flow cytometry (CFC) at time points throughout study.
  2. Anti-tumor effects of HER2-specific T cells will be determined by evaluating tumor response and progression using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
  3. The persistence of T cell immune augmentation in vivo after adoptive transfer of HER2-specific T cells will be evaluated by follow-up blood draws which will be analyzed for presence of HER2-specific T cells every 2 months for 1 year following the last infusion.
Related Publications
Tumor antigen-specific T-cell expansion is greatly facilitated by in vivo priming
Dang Y, Knutson KL, Goodell V, dela Rosa C, Salazar LG, Higgins D, Childs J, Disis ML
Clin Cancer Research 13(6):1883-91, 2007
 
Clinical Description
 
ClinicalTrials.gov Identifier: NCT00228358
 
Page last updated 4/27/09