Single-step Antigen Loading and TLR Activation of Dendritic Cells in Melanoma Patients
This study is ongoing, but not recruiting participants.
Sponsor:
Radboud University
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
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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
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 Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal |
Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas |
ClinicalTrials.gov processed this record on May 23, 2013