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Phase I/II Study of Vaccination With Antigen Loaded Dendritic Cells (DCs) in Patients With Inoperable Stage III and Stage IV Melanoma

Primary Purpose

Melanoma

Status
Terminated
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
Dendritic cell application
Sponsored by
Prof. Dr. Silke Gillessen
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring melanoma, dendritic cells, peptide, Melan-A

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
  • Neutrophile count >1500/ul and thrombocytes >100 000/ul
  • Creatinine <1.5 of upper normal level
  • Adequate liver function with bilirubin <2 of upper normal level, alanine aminotransferase (ALAT) and aspartate aminotransaminase (ASAT) < 3 x upper normal level
  • Clinically significant (i.e. active) cardiovascular disease: Cardiovascular accident (CVA)/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure or serious cardiac arrythmia requiring medication
  • absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • before patient registration, informed consent must be given according to International Conference on Harmonization (ICH)- Good Clinical Practice (GCP), and national/local regulations

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
  • Lack of availability of the patient for immunological and clinical follow-up assessment.
  • Coagulation or bleeding disorders
  • Rapidly progressing disease

Sites / Locations

  • Cantonal Hospital St.Gallen

Outcomes

Primary Outcome Measures

Toxicity as defined by NCI Common Toxicity Criteria Version 3.0 (App I)
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 Outcome Measures

Response rates in case of measurable disease
Three indicator lesions that are measurable in 2 diameters will be assessed radiologically. If there are not three measurable lesions, only the measurable lesions will be assessed.

Full Information

First Posted
September 13, 2013
Last Updated
September 13, 2013
Sponsor
Prof. Dr. Silke Gillessen
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1. Study Identification

Unique Protocol Identification Number
NCT01944709
Brief Title
Phase I/II Study of Vaccination With Antigen Loaded Dendritic Cells (DCs) in Patients With Inoperable Stage III and Stage IV Melanoma
Official Title
Phase I/II Study of Vaccination With Antigen Loaded Dendritic Cells (DCs) in Patients With Inoperable Stage III and Stage IV Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Terminated
Why Stopped
Progressive Disease
Study Start Date
August 2006 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Prof. Dr. Silke Gillessen

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
melanoma, dendritic cells, peptide, Melan-A

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
Dendritic cell application
Primary Outcome Measure Information:
Title
Toxicity as defined by NCI Common Toxicity Criteria Version 3.0 (App I)
Description
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.
Time Frame
24 hours
Secondary Outcome Measure Information:
Title
Response rates in case of measurable disease
Description
Three indicator lesions that are measurable in 2 diameters will be assessed radiologically. If there are not three measurable lesions, only the measurable lesions will be assessed.
Time Frame
12 weeks, 20 weeks, 28 weeks
Other Pre-specified Outcome Measures:
Title
Peptide specific cellular immunity: Analyses of peptide specific peripheral blood lymphocytes (PBL) by - tetramer method (flow cytometry) - interferon-gamma ELISPOT
Description
Monitoring of immune responses in peripheral blood mononuclear cells (PBMC) via enzyme-linked immunospot (ELISPOT) and Tetramer-staining.
Time Frame
6 weeks, 12 weeks, 20 weeks, 28 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 Neutrophile count >1500/ul and thrombocytes >100 000/ul Creatinine <1.5 of upper normal level Adequate liver function with bilirubin <2 of upper normal level, alanine aminotransferase (ALAT) and aspartate aminotransaminase (ASAT) < 3 x upper normal level Clinically significant (i.e. active) cardiovascular disease: Cardiovascular accident (CVA)/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure or serious cardiac arrythmia requiring medication absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial before patient registration, informed consent must be given according to International Conference on Harmonization (ICH)- Good Clinical Practice (GCP), and national/local regulations 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 Lack of availability of the patient for immunological and clinical follow-up assessment. Coagulation or bleeding disorders Rapidly progressing disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Silke Gillessen, MD
Organizational Affiliation
Cantonal Hospital St. Gallen, Dept. Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cantonal Hospital St.Gallen
City
St.Gallen
ZIP/Postal Code
9007
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

Phase I/II Study of Vaccination With Antigen Loaded Dendritic Cells (DCs) in Patients With Inoperable Stage III and Stage IV Melanoma

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