Clinical trial NCT01308294: Immunotherapy of HLA-A2 Positive Stage II-IV Melanoma Patients
Official title: Vaccination of Melanoma Patients (Stage II-IV) With ImmuFact IMP321, Tumor Antigenic Peptides and Montanide
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Melanoma
Keywords: Melanoma
Stage II-IV
Immunotherapy
Vaccination
HLA class I and II tumor-specific peptides
IMP321
Montanide ISA-51
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
Collaborators: name: Immutep S.A.S.
First posted: 2011-03-04
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: open label, non comparative study in patients suffering from stage II, III or IV melanoma
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether vaccination with tumor antigenic peptides and both IMP321/LAG-3 and Montanide adjuvants can induce an immune response in melanoma patients and to assess the safety and tolerability of this vaccination. Tumor responses following this vaccination will also be documented.

Detailed description: The primary objective of this study is:

* to evaluate melanoma antigen specific immune response induced by this vaccination with tumor antigenic peptides derived from MAGE-A3 (Melanoma Antigen family A3) (MHCI: MAGE-A3.A2 and MHCII: MAGE-A3.DP4), NY-ESO-1 (New York Esophageal squamous cell carcinoma antigen-1), Melan A (analog ELA and native EAA) and NA-17A with IMP321 (ImmuFact)/ LAG-3Ig (Lymphocyte activation gene-3 immunoglobulin-like domains) as adjuvant/immunostimulant, formulated with Montanide ISA-51.
* to assess the safety and tolerability of this vaccination

The secondary objective is to document tumor responses in patients following this vaccination.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed stage II, III or IV melanoma patients.
* Tumor expression of Melan-A.
* Human leukocyte antigen-A2 (HLA-A2) positive.
* Expected survival of at list 3 months.
* Karnofsky scale performance status of 70 % or more.
* Age ≥ 18 years.
* Able to give a written informed consent.
* The following laboratory results:

Hemoglobin ≥ 100g/L, Neutrophil count ≥ 1.5 x 109/L, Lymphocyte count ≥ 0.5 x 109/L, Platelet count ≥ 100 x 109/L, Serum creatinine ≤ 2 mg/dL (0.18mmol/L), Serum bilirubin ≤ 2mg/dL (0.034mmol/L), Granulocyte count \> 2.5x109/L, Aspartate Amino Transférase (ASAT), Alanine Amino Transferase (ALAT) \< 2.5 x upper limit of normal, Activated Partial Thromboplastin Time (aPTT) within the normal ranges ±25%, Thromplastin (TP) ≥ 80%

Exclusion Criteria:

* Clinically significant heart disease.
* Serious illness, eg. serious infections requiring antibiotics, uncontrolled peptic ulcer, or central nervous system disorders.
* History of immunodeficiency disease or autoimmune disease.
* Metastatic disease to the central nervous system, unless treated and stable.
* Known HIV positivity.
* Known seropositivity for hepatitis B surface antigen.
* Concomitant treatment with steroids, antihistamine drugs. Topical or inhalation steroids are permitted.
* Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
* Pregnancy or lactation.
* Women of childbearing potential not using a medically acceptable means of contraception.
* Psychiatric or addictive disorders that may compromise the ability to give informed consent.
* Lack of availability of the patient for immunological and clinical follow-up assessment.
* Coagulation or bleeding disorders.
* Kidney dysfunction with creatinine \> 2 X the upper limit of the normal value.
* Reported strong (allergic) reactions to previous vaccination.

Primary outcomes:
measure: Ex Vivo Frequency of Melan-A Specific CD8+T Cells
timeFrame: Melan-A specific CD8+ T cells were measured in PBMC collected at the end of Cycle 1 (Week 7), end of Cycle 2 (Week 25), end of Cycle 3 (Week 40), and Follow-up (6 to 18 months after the end of Cycle 3).
measure: In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Interferon-gamma (IFN-γ)
timeFrame: MAGE A3.DP4 specific CD4+ T cells producing IFN-γ were measured in PBMC collected at the end of Cycle 1 (Week 7), end of Cycle 2 (Week 25), end of Cycle 3 (Week 40), and Follow-up (6 to 18 months after the end of Cycle 3).
measure: In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Tumor Necrosis Factor-alpha (TNF-α)
timeFrame: MAGE A3.DP4 specific CD4+ T-cells producing TNF-α were measured in PBMC collected at the end of Cycle 1 (Week 7), end of Cycle 2 (Week 25), end of Cycle 3 (Week 40), and Follow-up (6 to 18 months after the end of Cycle 3).
measure: In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells
timeFrame: MAGE A3.DP4 specific CD4+ T cells were measured in PBMC collected at the end of Cycle 1 (Week 7), end of Cycle 2 (Week 25), end of Cycle 3 (Week 40) and Follow-up (6 to 18 months after the end of Cycle 3).
measure: In Vitro Frequency of Melan-A-specific CD8+T Cells After Stimulation
timeFrame: In vitro stimulated Melan-A specific CD8+ T cells were measured in PBMC collected at the end of Cycle 1 (Week 7), end of Cycle 2 (Week 25), end of Cycle 3 (Week 40) and Follow-up (6 to 18 months after the end of Cycle 3).
measure: In Vitro Frequency of NY-ESO-1-specific CD8+ T Cells
timeFrame: In vitro stimulated NY-EYO-1 specific CD8+ T cells were measured in PBMC collected at the end of Cycle 1 (Week 7), end of Cycle 2 (Week 25), end of Cycle 3 (Week 40), and Follow-up (6 to 18 months after the end of Cycle 3).
Secondary outcomes:
measure: Tumor Response
timeFrame: Change from baseline in tumor response at the end of Cycle 1 (Week 7), end of Cycle 2 (Week 25) and end of Cycle 3 (Week 40)
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Oncology Department, CHUV
state: Vaud
Study officials:
affiliation: Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne
name: Olivier Michielin, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sierro S, Romero P, Speiser DE. The CD4-like molecule LAG-3, biology and therapeutic applications. Expert Opin Ther Targets. 2011 Jan;15(1):91-101. doi: 10.1517/14712598.2011.540563.
citation: Brignone C, Escudier B, Grygar C, Marcu M, Triebel F. A phase I pharmacokinetic and biological correlative study of IMP321, a novel MHC class II agonist, in patients with advanced renal cell carcinoma. Clin Cancer Res. 2009 Oct 1;15(19):6225-31. doi: 10.1158/1078-0432.CCR-09-0068. Epub 2009 Sep 15.
citation: Speiser DE, Romero P. Molecularly defined vaccines for cancer immunotherapy, and protective T cell immunity. Semin Immunol. 2010 Jun;22(3):144-54. doi: 10.1016/j.smim.2010.03.004. Epub 2010 Apr 21.
citation: Legat A, Maby-El Hajjami H, Baumgaertner P, Cagnon L, Abed Maillard S, Geldhof C, Iancu EM, Lebon L, Guillaume P, Dojcinovic D, Michielin O, Romano E, Berthod G, Rimoldi D, Triebel F, Luescher I, Rufer N, Speiser DE. Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients--Report of a Phase I/IIa Clinical Trial. Clin Cancer Res. 2016 Mar 15;22(6):1330-40. doi: 10.1158/1078-0432.CCR-15-1212. Epub 2015 Oct 23.