Safety Study of a Dendritic Cell-based Cancer Vaccine in Melanoma

Phase 1

Completed

• Conditions: Melanoma; Tumor Vaccines; Effects of Immunotherapy
• Interventions: Biological: GeniusVac-Mel4

• Registration Number: NCT01863108
• Lead Sponsor: University Hospital, Grenoble

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.

Study Timeline

• Study First Submitted: 2013-05-22
• Study First Submitted QC: 2013-05-22
• Study First Posted: 2013-05-27
• Study Start: 2013-06
• Primary Completion: 2017-03-23
• Study Completion: 2017-03-23
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-10
• Last Update Posted: 2017-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GeniusVac-Mel4	GeniusVac-Mel4	Sub-cutaneous injections of GeniusVac-Mel4 in patients with melanoma.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).
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)

Trial Locations

Locations (1)

Grenoble University Hospital; 🇫🇷 Grenoble, France