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

NCT01530698 | Completed Phase 1

• 3 other identifiers: NL2009-015737-732009-015737-73AMO2009-084
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• The primary objective of the study isto investigate immunological responses upon vaccination

  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

  3 years

• The second primary objective is the toxicity of TLR-DC and Trimix-DC

  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

  3 years

Secondary Outcomes (1)

• clinical efficacy

  5 years

Study Arms (2)

single step DC treatment

EXPERIMENTAL

vaccination with autologous dendritic cells treated with mRNA electroporation for single-step antigen loading and TLR activation (TriMix-DC)

Biological: autologous dendritic cell vaccine

two step DC treatment

ACTIVE COMPARATOR

vaccination with autologous dendritic cells treated with mRNA electroporation for antigen loading and separately for TLR activation

Biological: autologous dendritic cell vaccine

Interventions

autologous dendritic cell vaccine BIOLOGICAL

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

single step DC treatment

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
• 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)

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 symptomatic 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

• Radboud University Nijmegen Medical Centre, Dept of Medical Oncology
• Nijmeegs Offensief Tegen Kanker
• Central Committee on Research involving Human Subjects (CCMO), The Netherlands

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 Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 31, 2011
• First Posted: February 10, 2012
• Study Start: April 1, 2010
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: April 17, 2017

Record last verified: 2014-11

Locations

NL (1)