Phase I/II Study of Vaccination With Antigen Loaded Dendritic Cells (DCs) in Patients With Inoperable Stage III and Stage IV Melanoma
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Melanoma
- Sponsor
- Prof. Dr. Silke Gillessen
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Toxicity as defined by NCI Common Toxicity Criteria Version 3.0 (App I)
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief Summary
The prognosis of patients with metastatic melanoma is poor and current available treatments are limited. Identification of a number of melanoma-specific tumor antigens that are shared by tumors from different patients, provides attractive targets for immune-based therapies (http://www.bioinfo.org.cn/hptaa/). Different approaches like DNA-/RNA-vaccines, peptide vaccines and dendritic cell (DC) vaccines are under investigation to induce peptide-specific immune responses. In various animal models and in clinical trials it was shown that the most potent induction of anti tumor-specific killer cells was achieved with DC vaccination. DCs are professional antigen presenting cells (APC) that are critical in the initiation of cellular responses in naïve T lymphocytes, in vivo. They are armed with all the molecules needed for the induction of immune responses and have the capacity to migrate into secondary lymphatic organs. In vitro generated dendritic cells are loaded with tumor derived peptides and injected subcutaneously. The concept is to induce or to propagate already existing tumor specific killer T cells.
Investigators
Prof. Dr. Silke Gillessen
lead consultant
Cantonal Hospital of St. Gallen
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed melanoma
- •Inoperable Stage III or Stage IV melanoma
- •Tumor expression of Melan-A and/or NY-Eso-1 by immunohistochemistry
- •Human leukocyte antigen (HLA)-A0201 positivity (flow cytometry and PCR)
- •Life expectancy more than three months
- •Full recovery from surgery
- •Karnofsky scale performance status of 70% or more (App II)
- •One prior chemo- or cytokine based therapy is allowed
- •Age \> 18 years
- •No uncontrolled infections
Exclusion Criteria
- •Presently clinically significant heart disease (NYHA Class III or IV)
- •Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders or uncontrolled peptic ulcer, or seizure or central nervous system disorders
- •History of immunodeficiency disease or severe autoimmune disease
- •Metastatic disease to the central nervous system
- •HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) (test required) or any other severe uncontrolled infection
- •Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry
- •Concomitant treatment with steroids or antihistamine drugs. Topical or inhalational steroids are permitted
- •Participation in any other clinical trial involving another investigational agent within 6 weeks prior to enrollment
- •Pregnancy or lactation
- •Women of childbearing potential not using a medically acceptable means of contraception
Outcomes
Primary Outcomes
Toxicity as defined by NCI Common Toxicity Criteria Version 3.0 (App I)
Time Frame: 24 hours
If any grade III or IV toxicity occurs within 24 hours of the vaccine treatment, no further vaccinations will be given. Grade III or IV toxicities arising later will only lead to treatment termination if the toxicity is clinically significant and can be attributed to the vaccination.
Secondary Outcomes
- Response rates in case of measurable disease(12 weeks, 20 weeks, 28 weeks)