Effects of Immunotherapy, Melanoma, Tumor Vaccines
Conditions
Keywords
Melanoma, Immunotherapy, Dermatology, cancer vaccine, Plasmacytoid dendritic cell line, Advanced Medicinal Therapy Product, allogeneic
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.
Interventions
BIOLOGICALGeniusVac-Mel4
Multiple sub-cutaneous injections (1 injection weekly during 3 weeks) of GeniusVac-Mel4 (3 increasing dose groups) in patients with melanoma
Sponsors
Etablissement Français du Sang
Institut National de la Santé Et de la Recherche Médicale, France
Université Joseph Fourier
University Hospital, Grenoble
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability and safety of a multiple sub-cutaneous injections of GeniusVac-Mel4. | 1 year | Safety and tolerance is monitored by performing clinical laboratory tests, assessments of vital signs, full clinical examination, occurrence of adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the immune response | 1 year | The induction of an immune response is evaluated at several time points by measuring : * The frequency of the T lymphocytes specific for each peptide used in the protocol. * The functionality of these T-cells (cytotoxicity and IFN-g secretion) |
| Evaluation of the clinical response | 1 year | The evolution of the disease will be determined with a clinical examination and scanner exams. The overall tumor response will be evaluated in accordance RECIST 1.1 and immune-related response criteria (irRC). |
Countries
France
Outcome results
None listed