Single-step Antigen Loading and TLR Activation of Dendritic Cells in Melanoma Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Radboud University.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Kees Punt, Radboud University
ClinicalTrials.gov Identifier:
NCT01530698
First received: March 31, 2011
Last updated: February 9, 2012
Last verified: February 2012
  Purpose

Objectives: This is an exploratory study, consisting of two parts. In part I dose escalation is performed and the primary objective is the safety of different doses of TLR-DC and Trimix DC. In part II Trimix DC vaccination will be compared with TLR-DC vaccination and the primary objective of this part is the immunological response, with toxicity and clinical efficacy being secondary objectives. These studies will provide important data on the safety and immunological effects of TLR-DC and Trimix DC.

Study design: Part I of this study is an open label dose escalation study. Part II of this study is an open label randomized phase II study.

Study population: Our study population consists of melanoma patients, with proven expression of melanoma associated tumor antigens gp100 and tyrosinase. Melanoma patients with regional lymph node metastasis in whom a radical lymph node dissection is performed within 2 months of inclusion in this study (further referred to as stage III) and melanoma patients with measurable distant metastases (further referred to as stage IV) will be included.


Condition Intervention Phase
Melanoma
Biological: autologous dendritic cell vaccine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Single-step Antigen Loading and TLR Activation of Dendritic Cells by mRNA Electroporation for Vaccination in Stage III and IV Melanoma Patients

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • The primary objective of the study isto investigate immunological responses upon vaccination [ Time Frame: 3 years ]
    The immunological response induced with TLR-DC and Trimix DC loaded with mRNA encoding melanoma-associated tumor antigens (gp100 and tyrosinase) will be evaluated by using 1. tetramer screening of skin-test biopsy derived cell-cultures and peripheral blood, 2. cytokine-bead assay to measure specific cytokine production of skin-test biopsy derived cell-cultures upon differential stimulation and 3. KLH-specific antibody and proliferative responses

  • The second primary objective is the toxicity of TLR-DC and Trimix-DC [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    toxicity will be reported with regard to 1. flu-like symptoms, 2. local injection site reaction and 3. other signs and symptoms, graded according to CTC version 3.0, numbers of patients and CTC grade will be reported


Secondary Outcome Measures:
  • clinical efficacy [ Time Frame: 5 years ]
    progression free survival


Estimated Enrollment: 35
Study Start Date: April 2010
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: single step DC treatment
autologous dendritic cells treated with mRNA electroporation for single-step antigen loading and TLR activation (TriMix-DC)
Biological: autologous dendritic cell vaccine
Autologous monocyte-derived dendritic cells electroporated with mRNA encoding gp100 and tyrosinase (for antigen loading), active TLR4 and CD70 (for activation). Dendritic cells are vaccinated intranodally 3 times with biweekly intervals every 6 months, if no signs of progression, for a total of 9 vaccinations
Active Comparator: two step DC treatment
autologous dendritic cells treated with mRNA electroporation for antigen loading and separately for TLR activation
Biological: autologous dendritic cell vaccine
Autologous monocyte-derived dendritic cells electroporated with mRNA encoding gp100 and tyrosinase and matured with either cytokines or TLR ligands. Dendritic cells are vaccinated intranodally 3 times with biweekly intervals every 6 months, if no signs of progression, for a total of 9 vaccinations

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Criteria

Inclusion Criteria:

(All patients):

  • histologically documented evidence of melanoma
  • stage III or IV melanoma according to the 2001 AJCC criteria
  • melanoma expressing gp100 (compulsory) and tyrosinase (non-compulsory)
  • WHO performance status 0-1 (Karnofsky 100-70)
  • life expectancy ≥ 3 months
  • age 18-70 years
  • no clinical signs or symptoms of CNS metastases
  • WBC > 3.0x10e9/l, lymphocytes > 0.8x10e9/l, platelets > 100x10e9/l, serum creatinine < 150 µmol/l, serum bilirubin < 25 µmol/l
  • normal serum LDH (< 450 U/l)
  • expected adequacy of follow-up
  • no pregnant or lactating women
  • written informed consent

(Stage III melanoma)

  • radical regional lymphnode dissection is performed (Stage IV melanoma)
  • at least one unidimensional measurable target lesions according to RECIST, not previously irradiated, and no significant symptoms of disease requiring other palliative treatments

Exclusion Criteria:

  • prior chemotherapy, immunotherapy or radiotherapy < 4 weeks prior to planned vaccination or presence of treatment-related toxicity
  • history of any second malignancy in the previous 5 years, with the exception of adequately treated basal cell carcinoma or carcinoma in situ of the cervix
  • serious active infections, HbsAg or HIV positive or autoimmune diseases or organ allografts
  • concomitant use of immunosuppressive drugs
  • known allergy to shell fish (since it contains KLH)
  • rapidly progressive symptomatic disease
  • any serious clinical condition that may interfere with the safe administration of DC
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01530698

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: C.J.A. Punt, prof.dr. Radboud University
  More Information

Additional Information:
No publications provided

Responsible Party: Kees Punt, professor, Radboud University
ClinicalTrials.gov Identifier: NCT01530698     History of Changes
Other Study ID Numbers: NL2009-015737-73, 2009-015737-73, AMO2009-084
Study First Received: March 31, 2011
Last Updated: February 9, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
dendritic cell vaccination
melanoma
toll like receptor ligands
mRNA electroporation
vaccines

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 22, 2014