NCT00228358

Cyclophosphamide or Denileukin Diftitox Followed By Expanding a Patient's Own T Cells in the Laboratory in Treating Patients With HER-2/Neu Overexpressing Metastatic Breast Cancer, Ovarian Cancer, or Non-Small Cell Lung Cancer Previously Treated With HER-2/Neu Vaccine

A Phase I Study of Infusion of HER-2/Neu Specific T Cells in Patients With Advanced Stage HER-2/Neu Expressing Cancers Who Have Received a HER-2/Neu Vaccine

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: University of Washington · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the safety and the ability to expand laboratory-treated T cells when given together with cyclophosphamide or denileukin diftitox in treating patients with human epidermal growth factor receptor (HER)-2/neu overexpressing metastatic breast cancer, ovarian cancer, or non-small cell lung cancer previously treated with HER-2/neu vaccine. Laboratory-expanded T cells may help the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapy, such as denileukin diftitox, may stimulate the immune system in different ways and stop tumor cells from growing. Giving laboratory-treated T cells together with cyclophosphamide or denileukin diftitox may allow the immune system to kill more tumor cells

Detailed description

PRIMARY OBJECTIVES: I. To assess the feasibility of expanding HER2 specific T cells ex vivo for infusion into subjects who have advanced HER2 overexpressing cancer. II. To assess the toxicity associated with infusing autologous HER2 specific T cells into patients using either a single dose of cyclophosphamide or ONTAK (denileukin diftitox) prior to T cell infusion. SECONDARY OBJECTIVES: I. To investigate to what extent HER2 specific T cell immunity can be boosted in individuals treated with a single dose of cyclophosphamide of ONTAK followed by infusion of autologous HER2 specific T cells. II. To investigate the potential anti-tumor effects of HER2 specific T cells in patients with HER2 overexpressing advanced-stage cancers. III. To evaluate how long tumor antigen specific T cell immune augmentation persists in vivo after a single dose of cyclophosphamide or ONTAK followed by infusion of autologous HER2 specific T cells. OUTLINE: This is a dose-escalation study of ex vivo-expanded HER2-specific T cells. Patients are assigned to 1 of 2 treatment groups. GROUP A: Patients receive low-dose cyclophosphamide intravenously (IV) on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20. GROUP B: Patients receive ONTAK (denileukin diftitox) IV over 1 hour on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20. After completion of study treatment, patients are followed periodically.

Conditions

• HER2-positive Breast Cancer
• Recurrent Breast Cancer
• Recurrent Non-small Cell Lung Cancer
• Recurrent Ovarian Epithelial Cancer
• Recurrent Ovarian Germ Cell Tumor
• Stage IV Breast Cancer
• Stage IV Non-small Cell Lung Cancer
• Stage IV Ovarian Epithelial Cancer
• Stage IV Ovarian Germ Cell Tumor

Interventions

Type	Name	Description
DRUG	ex vivo-expanded HER2-specific T cells	Laboratory-expanded T cells, given IV
DRUG	cyclophosphamide	Given IV
BIOLOGICAL	denileukin diftitox	Given IV
OTHER	flow cytometry	Intracellular cytokine staining (correlative study)
OTHER	immunoenzyme technique	ELIspot assay (correlative study)

Timeline

• Start date: 2003-06-01
• Primary completion: 2011-05-01
• First posted: 2005-09-28
• Last updated: 2014-11-11

Locations

1 site across 1 country: United States