Toll-like Receptor (TLR) Ligand Matured Dendritic Cell Vaccination in Melanoma Patients

NCT00940004 | Completed Phase 1

• 2 other identifiers: NL22750.000.08KUN2006-3699
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: This is an exploratory study, consisting of two parts. In part I a dose escalation is performed and the primary objective is the safety of different doses of TLR-dendritic cell (TLR-DC). In part II TLR-DC vaccination will be compared with cytokine-matured DC vaccination and the primary objective of this part is the immunological response to TLR-DC vaccination, with toxicity and clinical efficacy being secondary objectives. These studies will provide important data on the safety and immunological effects of TLR-matured DC. Study design: This study is an open label prospective exploratory intervention study. Study population: The investigators' study population consists of HLA-A2.1 positive 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 planned or 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.

Conditions

Melanoma

Keywords

dendritic cell vaccination; melanoma; toll like receptor ligands; vaccines

Outcome Measures

Primary Outcomes (1)

• Toxicity of TLR-matured DC (part I) and immunological response upon vaccination with TLR-matured DC (part II)

  3 years

Secondary Outcomes (2)

• vaccination related toxicity

  5 years

• clinical efficacy (progression free survival)

  5 years

Study Arms (2)

cytokine matured DC

ACTIVE COMPARATOR

vaccination with autologous dendritic cells matured with standard cytokine cocktail and electroporated with mRNA encoding tumor associated antigens

Biological: autologous dendritic cell vaccination

TLR ligand matured DC

EXPERIMENTAL

vaccination with autologous TLR-ligand matured dendritic cells electroporated with mRNA encoding tumor associated antigens

Biological: autologous dendritic cell vaccination

Interventions

autologous dendritic cell vaccination BIOLOGICAL

Autologous monocyte-derived dendritic cells electroporated with mRNA encoding gp100 and tyrosinase and matured with either cytokines or TLR ligands. Dendritic cells are vaccinated intradermal/intravenously 3 times with biweekly intervals every 6 months, if no signs of progression, for a total of 9 vaccinations.

TLR ligand matured DC; cytokine matured DC

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients:
• histologically documented evidence of melanoma
• stage III or IV melanoma according to the 2001 AJCC criteria
• HLA-A2.1 phenotype 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 \> 3.0x109/l, lymphocytes \> 0.8x109/l, platelets \> 100x109/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
• And in addition for Part I + II:
• stage III melanoma: radical regional lymphnode dissection is planned or performed

You may not qualify if:

• 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 disease
• any serious clinical condition that may interfere with the safe administration of DC

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6500HB, Netherlands

Location

Related Links

• home page Department of Medical Oncology

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• C.J.A. Punt, prof.dr.

  Radboud University Nijmegen Medical Centre, dept of Medical Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2009
• First Posted: July 15, 2009
• Study Start: June 1, 2009
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: April 17, 2017

Record last verified: 2014-11

Locations

NL (1)