Clinical trial NCT01863108: Safety Study of a Dendritic Cell-based Cancer Vaccine in Melanoma
Official title: Dose-escalation Study to Assess the Safety and Tolerability of Sub-cutaneous Injections of a Peptide-loaded Plasmacytoid Dendritic Cell Line (GeniusVac-Mel4) in Patients With Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Tumor Vaccines
Effects of Immunotherapy
Keywords: Melanoma
Immunotherapy
Dermatology
cancer vaccine
Plasmacytoid dendritic cell line
Advanced Medicinal Therapy Product
allogeneic
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Etablissement Français du Sang
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Université Joseph Fourier
First posted: 2013-05-27
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of multiple sub-cutaneous injections of GeniusVac-Mel4, a dendritic cell-based cancer vaccine, in patients with melanoma. The secondary objectives are to determine immune response and clinical efficacy of such injections in patients with melanoma.

Detailed description: GeniusVac-Mel4 is a drug product composed of an irradiated allogeneic plasmacytoid dendritic cell (PDC) line loaded with 4 melanoma peptides derived from Melan-A, gp100, Tyrosinase or Mage-A3. This cell line is HLA-A\*02:01, a phenotype found in 40% of the European population. This approach exploits the PDC line high capacity of boosting anti-tumor cytotoxic response against melanoma antigens in HLA-A\*02:01 melanoma patients. In the preclinical studies, a strong proof of concept was brought. Indeed, the GeniusVac-Mel4 capacity to induce high number of cytotoxic antitumor T-cells was shown in melanoma model, both in vivo in humanized mice and ex vivo with patients' PBMC (peripheral blood mononuclear cells) (Aspord et al 2010 and 2012).

It is planned to include patients in three dose-escalating groups (4, 20, 60 millions of GeniusVac-Mel4 cells). At least, 3 patients will be recruited in each dose group of the trial.

Eligibility criteria: Inclusion Criteria:

* Patients with histologically confirmed metastatic melanoma (at stage IIIC or stage IV under the AJCC 2009 classification not surgically resectable.
* Patients who do not respond to at least one line of systemic treatment
* Male and female (with β-HCG negative test)
* Patients HLA-A\*0201
* Age \> 18 years
* Blood parameters (Hemoglobin ≥ 10g/dl, Leucocytes ≥ 4000/μl,Lymphocytes ≥ 1000/μl, Platelets ≥100.000/μl, creatinin ≤ 2.0mg/dl, bilirubin ≤ 2.0mg/dl, ASAT and ALAT ≤ 2.5 fold the upper normal level)
* OMS performance score \< 3
* Informed written consent.

Exclusion Criteria:

* Positive serology for HCV, HTLV, HIV, active hepatitis
* Protected persons according to French regulations articles L1121-5 to L1121-8 (Public Health Code)
* Non-pregnant women without effective contraception
* Any serious acute or chronic illness, for example: active infection, coagulation disorder.
* Presence of a second cancer in the 5 years preceding inclusion into the study with the exception of in situ cervical carcinoma or a cutaneous carcinoma or other melanoma.
* Intercurrent disease requiring corticosteroids.
* Any active autoimmune disease including insulin dependent diabetes mellitus. Vitiligo or autoimmune thyroid disease are not criteria for exclusion.
* Autoimmune eye disease.
* Evidence of immunosuppression for any reason
* Primary ocular melanoma
* Chemotherapy, immunotherapy or radiotherapy in the 4 weeks preceding inclusion (6 weeks in the case of nitroso-urea and mitomycin C).
* Treatment with drugs under development within 4 weeks.
* Cerebral metastases metastasis with the exception of: known metastasis previously treated by surgery or stereotactic radio-surgery, AND Cerebral metastasis, if still present, must be stable for at least 90 days before inclusion and documented with two consecutive MRI or scanner with contrast media, AND, asymptomatic
* Existence of any surgical or medical condition which, in the judgment of the Investigator, might interfere with this study.
* Patients who are not willing to comply with the provisions of this protocol.

Primary outcomes:
measure: Tolerability and safety of a multiple sub-cutaneous injections of GeniusVac-Mel4.
timeFrame: 1 year
Secondary outcomes:
measure: Evaluation of the immune response
timeFrame: 1 year
measure: Evaluation of the clinical response
timeFrame: 1 year
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Grenoble University Hospital
Study officials:
affiliation: Etablissement Français du Sang/Grenoble University/ INSERM U823
name: Joel Plumas, PhD
role: STUDY_DIRECTOR
affiliation: University Hospital, Grenoble
name: Julie Charles, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aspord C, Leccia MT, Salameire D, Laurin D, Chaperot L, Charles J, Plumas J. HLA-A(*)0201(+) plasmacytoid dendritic cells provide a cell-based immunotherapy for melanoma patients. J Invest Dermatol. 2012 Oct;132(10):2395-2406. doi: 10.1038/jid.2012.152. Epub 2012 Jun 14.
citation: Aspord C, Charles J, Leccia MT, Laurin D, Richard MJ, Chaperot L, Plumas J. A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells. PLoS One. 2010 May 4;5(5):e10458. doi: 10.1371/journal.pone.0010458.