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Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients

Primary Purpose

Melanoma Stage III or IV

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
autologous dendritic cell vaccine
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma Stage III or IV focused on measuring Dendritic cells, Melanoma, Vaccine, Immunotherapy, RNA, Peptides

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: For both stage III and IV Histological proof of cutaneous melanoma Melanoma expressing both gp100 and tyrosinase, each in approximately 20% or more of cells by immunohistochemistry staining, HLA type A2 and/or A3, with known HLA-DR4 expression, WBC > 3.0 x 109/l, lymphocytes > 0.8 x 109/l, platelets > 100 x 109/l, serum creatinine < 150 μmol/l, serum bilirubin < 25 μmol/l. Expected adequacy of follow-up, Written informed consent. For Stage III only Stage III melanoma according to the 2001 AJCC criteria. Start of treatment within 2 months of lymph node dissection for melanoma stage III For stage IV only -Stage IV melanoma according to the 2001 AJCC criteria. Limited tumor burden; LDH < 2x upper limit of normal Exclusion Criteria: For both stage III and IV No autoimmune disorders, no concomitant use of immunosuppressive drugs, no serious concomitant disease, no serious active infections, no other malignancy in the past 5 years with the exception of curatively treated carcinoma in-situ of the cervix/squamous cell carcinoma of the skin, No known allergy to shell fish (contains KLH) are excluded. No pregnancy or lactation, For stage III only: No signs or symptoms of distant metastases as defined by normal history, physical examination, chest X-ray and serum LDH. No concomitant or previous systemic treatment for melanoma For stage IV only: No clinical signs of CNS metastases, in patients with a clinical suspicion of CNS metastases, a CT scan of the brain should be performed to exclude this. No prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed.

Sites / Locations

  • Radboud University Nijmegen Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

MHC Class I restricted epitopes

MHC Class I and II restricted epitopes

mRNA transfected DC

Arm Description

HLA-A2.1 patients are vaccinated with dendritic cells loaded with MHC Class I restricted epitopes of tumor antigens gp100 and tyrosinase

HLA-A2.1 and HLA-DR4 patients are vaccinated with dendritic cells loaded with MHC Class I and II restricted epitopes of tumor antigens gp100 and tyrosinase

HLA-A2.1 and/or HLA-DR4 patients are vaccinated with dendritic cells transfected with mRNA encoding tumor antigens gp100 and tyrosinase

Outcomes

Primary Outcome Measures

Immune response

Secondary Outcome Measures

Safety

Full Information

First Posted
October 21, 2005
Last Updated
September 28, 2009
Sponsor
Radboud University Medical Center
Collaborators
Dutch Cancer Society
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1. Study Identification

Unique Protocol Identification Number
NCT00243529
Brief Title
Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients
Official Title
In Vivo Responses of DC Vaccines Presenting HLA Class I and II Restricted Tumor Epitopes Either by Peptide-pulsing or mRNA Transfection in Melanoma Patients
Study Type
Interventional

2. Study Status

Record Verification Date
February 2009
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Radboud University Medical Center
Collaborators
Dutch Cancer Society

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Dendritic cells (DCs)are the most potent antigen-presenting cells of the immune system, as such they are able to direct the immune system specifically against cancer cells. Currently DCs are used in clinical vaccination studies and immunological and clinical responses have been observed. For inducing anti-tumor immunity, the DCs have to be loaded with tumor antigen (i.e. molecular structures that are presented by the tumor, that are recognized by the immune system). Currently most studies use tumor peptides (small protein fragments) for this purpose. This approach has several disadvantages: only patients with a certain HLA-type can be treated and the immune response that is induced by the vaccine is limited to the used peptides. These disadvantages do not exist when the DCs present antigen which is endogenously processed, for example after RNA transfection. For this reason we investigate the immunogenicity of DCs that are pulsed with peptides or transfected with mRNA encoding melanoma associated antigens in stage III and IV melanoma patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma Stage III or IV
Keywords
Dendritic cells, Melanoma, Vaccine, Immunotherapy, RNA, Peptides

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MHC Class I restricted epitopes
Arm Type
Active Comparator
Arm Description
HLA-A2.1 patients are vaccinated with dendritic cells loaded with MHC Class I restricted epitopes of tumor antigens gp100 and tyrosinase
Arm Title
MHC Class I and II restricted epitopes
Arm Type
Experimental
Arm Description
HLA-A2.1 and HLA-DR4 patients are vaccinated with dendritic cells loaded with MHC Class I and II restricted epitopes of tumor antigens gp100 and tyrosinase
Arm Title
mRNA transfected DC
Arm Type
Experimental
Arm Description
HLA-A2.1 and/or HLA-DR4 patients are vaccinated with dendritic cells transfected with mRNA encoding tumor antigens gp100 and tyrosinase
Intervention Type
Biological
Intervention Name(s)
autologous dendritic cell vaccine
Primary Outcome Measure Information:
Title
Immune response
Time Frame
first 10 years
Secondary Outcome Measure Information:
Title
Safety
Time Frame
first 10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: For both stage III and IV Histological proof of cutaneous melanoma Melanoma expressing both gp100 and tyrosinase, each in approximately 20% or more of cells by immunohistochemistry staining, HLA type A2 and/or A3, with known HLA-DR4 expression, WBC > 3.0 x 109/l, lymphocytes > 0.8 x 109/l, platelets > 100 x 109/l, serum creatinine < 150 μmol/l, serum bilirubin < 25 μmol/l. Expected adequacy of follow-up, Written informed consent. For Stage III only Stage III melanoma according to the 2001 AJCC criteria. Start of treatment within 2 months of lymph node dissection for melanoma stage III For stage IV only -Stage IV melanoma according to the 2001 AJCC criteria. Limited tumor burden; LDH < 2x upper limit of normal Exclusion Criteria: For both stage III and IV No autoimmune disorders, no concomitant use of immunosuppressive drugs, no serious concomitant disease, no serious active infections, no other malignancy in the past 5 years with the exception of curatively treated carcinoma in-situ of the cervix/squamous cell carcinoma of the skin, No known allergy to shell fish (contains KLH) are excluded. No pregnancy or lactation, For stage III only: No signs or symptoms of distant metastases as defined by normal history, physical examination, chest X-ray and serum LDH. No concomitant or previous systemic treatment for melanoma For stage IV only: No clinical signs of CNS metastases, in patients with a clinical suspicion of CNS metastases, a CT scan of the brain should be performed to exclude this. No prior chemotherapy, immunotherapy, or radiotherapy within three months before planned vaccination is allowed.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prof. C.J.A. Punt, MD, PhD
Organizational Affiliation
Radboud University Nijmegen Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Prof. G.J. Adema, PhD
Organizational Affiliation
Radboud University Nijmegen Medical Center/Nijmegen Center for Molecular Life Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Nijmegen Medical Center
City
Nijmegen
State/Province
PO Box 9101
ZIP/Postal Code
6500 HB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
16110035
Citation
de Vries IJ, Bernsen MR, Lesterhuis WJ, Scharenborg NM, Strijk SP, Gerritsen MJ, Ruiter DJ, Figdor CG, Punt CJ, Adema GJ. Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome. J Clin Oncol. 2005 Aug 20;23(24):5779-87. doi: 10.1200/JCO.2005.06.478.
Results Reference
background
PubMed Identifier
15477299
Citation
Lesterhuis WJ, de Vries IJ, Adema GJ, Punt CJ. Dendritic cell-based vaccines in cancer immunotherapy: an update on clinical and immunological results. Ann Oncol. 2004;15 Suppl 4:iv145-51. doi: 10.1093/annonc/mdh919. No abstract available.
Results Reference
background
PubMed Identifier
15122249
Citation
Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004 May;10(5):475-80. doi: 10.1038/nm1039.
Results Reference
background
PubMed Identifier
14613986
Citation
de Vries IJ, Lesterhuis WJ, Scharenborg NM, Engelen LP, Ruiter DJ, Gerritsen MJ, Croockewit S, Britten CM, Torensma R, Adema GJ, Figdor CG, Punt CJ. Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. Clin Cancer Res. 2003 Nov 1;9(14):5091-100.
Results Reference
background
PubMed Identifier
12517769
Citation
De Vries IJ, Krooshoop DJ, Scharenborg NM, Lesterhuis WJ, Diepstra JH, Van Muijen GN, Strijk SP, Ruers TJ, Boerman OC, Oyen WJ, Adema GJ, Punt CJ, Figdor CG. Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state. Cancer Res. 2003 Jan 1;63(1):12-7.
Results Reference
background
PubMed Identifier
12218781
Citation
de Vries IJ, Eggert AA, Scharenborg NM, Vissers JL, Lesterhuis WJ, Boerman OC, Punt CJ, Adema GJ, Figdor CG. Phenotypical and functional characterization of clinical grade dendritic cells. J Immunother. 2002 Sep-Oct;25(5):429-38. doi: 10.1097/00002371-200209000-00007.
Results Reference
background
PubMed Identifier
15766677
Citation
Adema GJ, de Vries IJ, Punt CJ, Figdor CG. Migration of dendritic cell based cancer vaccines: in vivo veritas? Curr Opin Immunol. 2005 Apr;17(2):170-4. doi: 10.1016/j.coi.2005.01.004.
Results Reference
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Links:
URL
http://www.umcn.nl
Description
Home page of the Radboud University Nijmegen Medical Centre

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Peptide-pulsed vs. RNA-transfected Dendritic Cell Vaccines in Melanoma Patients

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