Safety Study of a Dendritic Cell-based Cancer Vaccine in Melanoma (GeniusVac-Mel4)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University Hospital, Grenoble
Sponsor:
Collaborators:
Etablissement Français du Sang
Institut National de la Santé Et de la Recherche Médicale, France
Université Joseph Fourier
Information provided by (Responsible Party):
University Hospital, Grenoble
ClinicalTrials.gov Identifier:
NCT01863108
First received: May 22, 2013
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Tumor Vaccines
Effects of Immunotherapy
Biological: GeniusVac-Mel4
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:
  • Tolerability and safety of a multiple sub-cutaneous injections of GeniusVac-Mel4. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Safety and tolerance is monitored by performing clinical laboratory tests, assessments of vital signs, full clinical examination, occurrence of adverse events.


Secondary Outcome Measures:
  • Evaluation of the immune response [ Time Frame: 1 year ] [ Designated as safety issue: No ]

    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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 15
Study Start Date: June 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GeniusVac-Mel4
Sub-cutaneous injections of GeniusVac-Mel4 in patients with melanoma.
Biological: GeniusVac-Mel4
Multiple sub-cutaneous injections (1 injection weekly during 3 weeks) of GeniusVac-Mel4 (3 increasing dose groups) 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01863108

Contacts
Contact: Julie Charles, MD, PhD 0033 4 76 76 93 20 JCharles@chu-grenoble.fr

Locations
France
Grenoble University Hospital Recruiting
Grenoble, France, 38000
Sub-Investigator: Julie Charles, MD, PhD         
Sub-Investigator: Isabelle Templier, MD         
Sponsors and Collaborators
University Hospital, Grenoble
Etablissement Français du Sang
Institut National de la Santé Et de la Recherche Médicale, France
Université Joseph Fourier
Investigators
Study Director: Joel Plumas, PhD Etablissement Français du Sang/Grenoble University/ INSERM U823
Principal Investigator: Julie Charles, MD, PhD University Hospital, Grenoble
  More Information

Publications:
Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT01863108     History of Changes
Other Study ID Numbers: DCIC 11 19, 2012-003124-20
Study First Received: May 22, 2013
Last Updated: May 28, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Grenoble:
Melanoma
Immunotherapy
Dermatology
cancer vaccine
Plasmacytoid dendritic cell line
Advanced Medicinal Therapy Product
allogeneic

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 28, 2014