MelanomaPhase 1NCT00112242
Immunotherapy of Stage III/IV Melanoma Patients
A Phase 1 study testing Melan-A ELA + Montanide, Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide and Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG in people with Melanoma, run by Centre Hospitalier Universitaire Vaudois at 2 sites in Switzerland.
Trial summary
The purpose of this study is to determine whether vaccination with melanoma antigen peptides [Melan-A/Mart-1 (both EAA and ELA), NY-ESO-1b analog, Long NY-ESO-1 LP and MAGE-A10] and Montanide, CpG adjuvants and low dose rIL-2 can induce an immune response in melanoma patients and to assess the safety of this… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Melan-A ELA + Montanide, Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide and Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 2 sitesSwitzerland
- Study dates
- Feb 2004to Mar 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed stage III or stage IV melanoma with at least one metastatic lymph node and/or at least one in-transit metastasis. According to the AJCC rules, this includes all patients with stage IV and stage III. Patients with or without measurable disease may be included.
- Tumor expression of Melan-A by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis for patients of group I.
- Tumor expression of Melan-A and at least one of the tumor antigens MAGE-A10, NY-ESO-1, or LAGE-1 by rt-PCR analysis for patients of group II and III and for HLA-A2+ patients of groups IV and V. HLA-A2 negative patients of groups IV and V must only have NY-ESO-1 positive tumors to be eligible, while expression of Melan-A and MAGE-A10 is unimportant.
- If no frozen tissue is available, immunohistochemistry may be performed to detect tumor expression of Melan-A and NY-ESO-1.
- HLA-A2 positive (serological or molecular typing of Peripheral Blood Lymphocytes (PBL) for patients of groups 1 to 3. Patients of groups 4 and 5 may either be HLA-A2+ or HLA-A2-.
- Expected survival of at least five months.
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- Full recovery from surgery.
- Karnofsky scale performance status of 70% or more.
- The following laboratory results:
- Neutrophil count sup or equal 2.0 x 10^9/L Lymphocyte count sup or equal 0.5 x 10^9/L Platelet count sup or equal 100 x 10^9/L Creatinine ≤ 2 mg/dL (180 micromol/L) Bilirubin ≤ 2mg/dL (34 micromol/L) Granulocyte count > 2.5x10^9/L AST < 2x upper limit of normal aPTT: within the normal ranges of the laboratory ± 25 %
- Age > 18 years.
- Able to give written informed consent.
Who cannot join
- Clinically significant heart disease (NYHA Class III or IV).
- Other serious illnesses, e.g., serious infections requiring antibiotics, uncontrolled peptic ulcer, or central nervous system disorders with major dysfunction.
- History of immunodeficiency disease or autoimmune disease.
- Known HIV positivity.
- Known seropositivity for hepatitis B surface antigen.
- Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
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- Concomitant treatment with steroids, antihistamine drugs. Topical or inhalational 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.
- Metastatic disease to the central nervous system, unless treated and stable.
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites
Division of Oncology at the Geneva University Hospital
Geneva, 1211
Oncology Department, Lausanne University Hospital (CHUV) and University of Lausanne
Lausanne, Canton of Vaud, 1011
About this study
Official title: Vaccination of Patients With Stage III or IV Malignant Melanoma With Melanoma Antigen Peptides [Melan-A/Mart-1 Analog (ELA), NY-ESO-1b(A) Analog and MAGE-A10] and Montanide Adjuvant
The purpose of this study is to determine whether vaccination with melanoma antigen peptides [Melan-A/Mart-1 (both EAA and ELA), NY-ESO-1b analog, Long NY-ESO-1 LP and MAGE-A10] and Montanide, CpG adjuvants and low dose rIL-2 can induce an immune response in melanoma patients and to assess the safety of this vaccination.
Read the detailed description
Current peptide vaccines suffer from low efficiency, since they induce only weak immune activation. We have recently confirmed that in humans the immune response was readily detectable in local lymph nodes while no or only weak activation could be identified in circulating lymphocytes. Increased doses of antigen and adjuvant allow a better extension from local to systemic immune responses.
- Group 1 : vaccination with Melan-A analog (ELA) peptide + Montanide
- Group 2 : vaccination with Melan-A analog (ELA), NY-ESO-1b analog and MAGE-A10 peptides + Montanide
- Group 3: vaccination with Melan-A analog (both EAA and ELA), Mage-A10, NY-ESO-1 peptides+ Montanide + CpG adjuvant
- Group 4: vaccination with Melan-A (ELA), Mage-A10,long NY-ESO-1LP peptides + Montanide + CpG
- Group 5: vaccination with Melan-A (both EAA and ELA), Mage-A10, long NY-ESO-1 LP peptides + Montanide + CpG + low dose rIL-2
- Conditions
- Melanoma
- Being tested
- Melan-A ELA + Montanide, Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide, Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG, Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG, Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG+ IL-2
- Keywords
- Immunotherapy, Vaccination, Melanoma, Melan-A/Mart-1 peptide, MAGE-A10 peptide, NY-ESO-1 peptide, Montanide, CpG
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Melan-A ELA + MontanideBiological
A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.
Melan-A ELA + NY-ESO-1b + MAGE-A10 + MontanideBiological
A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.
Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpGBiological
A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.
Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpGBiological
A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.
Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG+ IL-2Biological
A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.
| Study group | Role | What they receive |
|---|---|---|
| 1. Melan-A ELA | Experimental | 500 mcg Melan-A ELA analog peptide + 1 ml Montanide ISA-51 Receives: Biological: Melan-A ELA + Montanide |
| 2. Melan-A ELA + NY-ESO-1b + MAGE-A10 | Experimental | 500 mcg Melan-A ELA analog peptide + 500 mcg NY-ESO-1b(A) analog peptide + 500 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 Receives: Biological: Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide |
| 3. Melan-A ELA + NY-ESO-1b + MAGE-A10 + CpG | Experimental | 500 mcg Melan-A ELA analog peptide + 500 mcg NY-ESO-1b(A) analog peptide + 500 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 + 2.5 mg CpG-7909/PF-3512676 Receives: Biological: Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG |
| 4. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG | Experimental | * If patient is HLA-A2 positive: 100 mcg Melan-A EAA native peptide (during first cycle) or 100 mcg ELA analog peptide (during other cycles) + 500 mcg NY-ESO-1lp long peptide + 100 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676
* If patient is HLA-A2 negative: 500 mcg NY-ESO-1lp long peptide+ 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 Receives: Biological: Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG |
| 5. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG+ IL-2 | Experimental | * If patient is HLA-A2 positive: 100 mcg Melan-A EAA native peptide (during first cycle) or 100 mcg ELA analog peptide (during other cycles) + 500 mcg NY-ESO-1lp long peptide + 100 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 + low dose IL-2
* If patient is HLA-A2 negative: 500 mcg NY-ESO-1lp long peptide+ 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 + low dose IL-2 Receives: Biological: Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG+ IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Mean Number of Adverse Events (Serious and Non Serious Events)
Safety of the vaccination was assessed according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) scale. The adverse events (AE) and serious adverse events (SAE) were registered at each study visit during the 3 vaccination cycles and boost cycles.
Measured: Change from baseline to end of Cycle 1 (3 months), end of Cycle 2 (8 months), end of Cycle 3 (13 months) and end of Boost Cycles (18 months to 23 months).
Fold Change From Baseline in ex Vivo Melan-A-specific CD8+ T Cells Frequency During the Vaccination Period
Ex vivo frequency of Melan-A-specific CD8+ T cells was measured by multimer technique (tetramer assay) in a multicolor flow cytometry analysis.
The fold change for each time point compared to baseline was calculated as: Melan-A-specific CD8+ T cell frequency at the time point/ Melan-A-specific CD8+ T cell frequency at baseline.
Significant T cell response is defined by at least 2-fold change of Melan-A-specific CD8+ T cell frequency as compared to pre-immunotherapy.
Measured: Fold change from baseline in Melan-A-specific CD8+T-cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months).
Fold Change From Baseline in ex Vivo Frequency of Melan-A-specific IFN-γ-secreting CD8+ T Cells During the Vaccination Period
Ex vivo frequency of Melan-A-specific CD8+ T cells producing IFN-γ (Interferon-gamma) was measured through the Enzyme-Linked Immunosorbent Spot (ELISpot) assay.
The fold change for each time point compared to baseline was calculated as: Melan-A-specific IFN-γ-secreting CD8+ T cell frequency at the time point/ Melan-A-specific IFN-γ-secreting CD8+ T cell frequency at baseline.
Measured: Fold change from baseline in Melan-A-specific IFN-γ-secreting CD8+T-cells frequency at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Fold Change From Baseline in ex Vivo Frequency of NY-ESO-1-specific CD8+ T Cells During the Vaccination Period
Ex vivo frequency of NY-ESO-1-specific CD8+ T cells was measured by multimer technique (tetramer assay) in a multicolor flow cytometry analysis.
The fold change for each time point compared to baseline was calculated as: NY-ESO-1-specific CD8+ T cell frequency at the time point/ NY-ESO-1-specific CD8+ T cell frequency at baseline.
Measured: Fold change from baseline in NY-ESO-1-specific CD8+T-cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Fold Change From Baseline in ex Vivo Frequency of NY-ESO-1-specific IFN-γ-secreting CD8+ T Cells During the Vaccination Period
Ex vivo frequency of NY-ESO-1-specific CD8+ T cells producing IFN-γ (Interferon-gamma) was measured through the Enzyme-Linked Immunosorbent Spot (ELISpot) assay.
The fold change for each time point compared to baseline was calculated as: NY-ESO-1-specific IFN-γ-secreting CD8+ T cell frequency at the time point/ NY-ESO-1-specific IFN-γ-secreting CD8+ T cell frequency at baseline.
Measured: Fold change from baseline in NY-ESO-1-specific IFN-γ-secreting CD8+T-cells frequency at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Fold Change From Baseline in ex Vivo Frequency of MAGE-A10-specific CD8+ T Cells During the Vaccination Period
Ex vivo frequency of MAGE-A10-specific CD8+ T cells was measured by multimer technique (tetramer assay) in a multicolor flow cytometry analysis.
The fold change for each time point compared to baseline was calculated as: MAGE-A10-specific CD8+ T cell frequency at the time point/ MAGE-A10-specific CD8+ T cell frequency at baseline.
Measured: Fold change from baseline in MAGE-A10-specific CD8+T-cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Fold Change From Baseline in ex Vivo Frequency of MAGE-A10-specific IFN-γ-secreting CD8+ T Cells During the Vaccination Period
Ex vivo frequency of MAGE-A10-specific CD8+ T cells producing IFN-γ (Interferon-gamma) was measured through the Enzyme-Linked Immunosorbent Spot (ELISpot) assay.
The fold change for each time point compared to baseline was calculated as: MAGE-A10-specific IFN-γ-secreting CD8+ T cell frequency at the time point/ MAGE-A10-specific IFN-γ-secreting CD8+ T cell frequency at baseline.
Measured: Fold change from baseline in MAGE-A10-specific IFN-γ-secreting CD8+T-cells frequency at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Percentage of in Vitro Stimulated NY-ESO-1 Lp-specific IFN-γ/TNF-α -Secreting CD4+ T Cells During the Vaccination Period
For each patient, total CD4+ T-cells were stimulated in the presence of peptide NY-ESO-1 long peptide (lp). After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged. The activation of NY-ESO-1 long peptide (lp)-specific CD4+ T cells were analyzed in vitro by Intracellular Cytokine Staining (ICS) via detection of IFN-γ (Interferon-gamma) and TNF-α (Tumor Necrosis Factor-alpha) producing cells.
Measured: Percentage of NY-ESO-1 lp-specific IFN-γ/TNF-α -secreting CD4+ T-cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Percentage of in Vitro Stimulated NY-ESO-1 Lp-specific IFN-γ/TNFα -Secreting CD8+ T Cells During the Vaccination Period
For each patient, total CD8+ T cells were stimulated in the presence of peptide NY-ESO-1 long peptide (lp). After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged. The activation of NY-ESO-1 long peptide (lp)-specific CD8+ T cells were analyzed in vitro by Intracellular Cytokine Staining (ICS) via detection of IFN-γ (Interferon-gamma) and TNF-α (Tumor Necrosis Factor-alpha) producing cells.
Measured: Percentage of NY-ESO-1 lp-specific IFN-γ/TNF-α -secreting CD8+ T cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Secondary outcomes (1)
Disease Status Assessment During the Vaccination Period
The disease status was assessed by computed tomography (CT) or positron emission tomography (PET)/CT at baseline and after the fourth vaccination of each cycle. During the "booster vaccines" period, imagery examinations were performed every 3 months for patients with measurable disease and every 6 months for patients with non measurable disease.
The tumor response was assessed according to the classification World Health Organization (WHO) 1979 and defined as:
- No Evidence of Disease (NED)
- Stable disease (SD): Change in size of all measurable lesions (the sum of the products of the greatest and perpendicular parameters), of less than a 25% increase or 25% decrease from baseline for at least 4 weeks, without appearance of new lesions or progression of any lesion.
- Progressing disease (PD): Appearance of new tumors, or increase in size of any measurable tumor by at least 25% of the sum of the product of the greatest and perpendicular diameter.
Measured: Disease status at baseline, after cycle 1 (3 months), after cycle 2 (8 months), after cycle 3 (13 months) and if applicable after boost cycles (16 months, 19 months or 22 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2005 (estimated)
- Study startFeb 2004
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire VaudoisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Vaudois
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig Institute for Cancer Research
- Responsible party
- Principal investigator, Prof Olivier Michielin, M.D., Ph.D., Centre Hospitalier Universitaire Vaudois
- Investigators
- Olivier Michielin, MD PhD, Principal investigator, Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00112242
- Sponsor's protocol ID
- LUD 2001-003
- Status last verified
- Jun 2020
- First submitted
- 31 May 2005
- Last updated
- 18 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Baumgaertner P, Costa Nunes C, Cachot A, Maby-El Hajjami H, Cagnon L, Braun M, Derre L, Rivals JP, Rimoldi D, Gnjatic S, Abed Maillard S, Marcos Mondejar P, Protti MP, Romano E, Michielin O, Romero P, Speiser DE, Jandus C. Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8+ and CD4+ T-cell responses with multiple specificities including a novel DR7-restricted epitope. Oncoimmunology. 2016 Sep 9;5(10):e1216290. doi: 10.1080/2162402X.2016.1216290. eCollection 2016.
PubMed 27853637Hebeisen M, Schmidt J, Guillaume P, Baumgaertner P, Speiser DE, Luescher I, Rufer N. Identification of Rare High-Avidity, Tumor-Reactive CD8+ T Cells by Monomeric TCR-Ligand Off-Rates Measurements on Living Cells. Cancer Res. 2015 May 15;75(10):1983-91. doi: 10.1158/0008-5472.CAN-14-3516. Epub 2015 Mar 25.
PubMed 25808864Bordry N, Costa-Nunes CM, Cagnon L, Gannon PO, Abed-Maillard S, Baumgaertner P, Murray T, Letovanec I, Lazor R, Bouchaab H, Rufer N, Romano E, Michielin O, Speiser DE. Pulmonary sarcoid-like granulomatosis after multiple vaccinations of a long-term surviving patient with metastatic melanoma. Cancer Immunol Res. 2014 Dec;2(12):1148-53. doi: 10.1158/2326-6066.CIR-14-0143. Epub 2014 Oct 2.
PubMed 25277238Costa-Nunes C, Cachot A, Bobisse S, Arnaud M, Genolet R, Baumgaertner P, Speiser DE, Sousa Alves PM, Sandoval F, Adotevi O, Reith W, Protti MP, Coukos G, Harari A, Romero P, Jandus C. High-throughput Screening of Human Tumor Antigen-specific CD4 T Cells, Including Neoantigen-reactive T Cells. Clin Cancer Res. 2019 Jul 15;25(14):4320-4331. doi: 10.1158/1078-0432.CCR-18-1356. Epub 2019 Apr 23.
PubMed 31015344
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaccination of Patients With Stage III or IV Malignant Melanoma With Melanoma Antigen Peptides [Melan-A/Mart-1 Analog (ELA), NY-ESO-1b(A) Analog and MAGE-A10] and Montanide Adjuvant
- ClinicalTrials.gov ID
- NCT00112242
- Acronym / sponsor ID
- LUD 2001-003
- Conditions
- Melanoma
- Keywords
- Immunotherapy, Vaccination, Melanoma, Melan-A/Mart-1 peptide, MAGE-A10 peptide, NY-ESO-1 peptide, Montanide, CpG
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire VaudoisUniversity, hospital or other
- Collaborators
- Ludwig Institute for Cancer Research
- Study start
- Feb 2004
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 1 Jun 2005 (estimated)
- Results
- Posted 18 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether vaccination with melanoma antigen peptides [Melan-A/Mart-1 (both EAA and ELA), NY-ESO-1b analog, Long NY-ESO-1 LP and MAGE-A10] and Montanide, CpG adjuvants and low dose rIL-2 can induce an immune response in melanoma patients and to assess the safety of this vaccination.
Detailed description
Current peptide vaccines suffer from low efficiency, since they induce only weak immune activation. We have recently confirmed that in humans the immune response was readily detectable in local lymph nodes while no or only weak activation could be identified in circulating lymphocytes. Increased doses of antigen and adjuvant allow a better extension from local to systemic immune responses.
- Group 1 : vaccination with Melan-A analog (ELA) peptide + Montanide
- Group 2 : vaccination with Melan-A analog (ELA), NY-ESO-1b analog and MAGE-A10 peptides + Montanide
- Group 3: vaccination with Melan-A analog (both EAA and ELA), Mage-A10, NY-ESO-1 peptides+ Montanide + CpG adjuvant
- Group 4: vaccination with Melan-A (ELA), Mage-A10,long NY-ESO-1LP peptides + Montanide + CpG
- Group 5: vaccination with Melan-A (both EAA and ELA), Mage-A10, long NY-ESO-1 LP peptides + Montanide + CpG + low dose rIL-2
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1. Melan-A ELA | Experimental | Biological: Melan-A ELA + Montanide500 mcg Melan-A ELA analog peptide + 1 ml Montanide ISA-51 |
| 2. Melan-A ELA + NY-ESO-1b + MAGE-A10 | Experimental | Biological: Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide500 mcg Melan-A ELA analog peptide + 500 mcg NY-ESO-1b(A) analog peptide + 500 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 |
| 3. Melan-A ELA + NY-ESO-1b + MAGE-A10 + CpG | Experimental | Biological: Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG500 mcg Melan-A ELA analog peptide + 500 mcg NY-ESO-1b(A) analog peptide + 500 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 + 2.5 mg CpG-7909/PF-3512676 |
| 4. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG | Experimental | Biological: Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG* If patient is HLA-A2 positive: 100 mcg Melan-A EAA native peptide (during first cycle) or 100 mcg ELA analog peptide (during other cycles) + 500 mcg NY-ESO-1lp long peptide + 100 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 * If patient is HLA-A2 negative: 500 mcg NY-ESO-1lp long peptide+ 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 |
| 5. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG+ IL-2 | Experimental | Biological: Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG+ IL-2* If patient is HLA-A2 positive: 100 mcg Melan-A EAA native peptide (during first cycle) or 100 mcg ELA analog peptide (during other cycles) + 500 mcg NY-ESO-1lp long peptide + 100 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 + low dose IL-2 * If patient is HLA-A2 negative: 500 mcg NY-ESO-1lp long peptide+ 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 + low dose IL-2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed stage III or stage IV melanoma with at least one metastatic lymph node and/or at least one in-transit metastasis. According to the AJCC rules, this includes all patients with stage IV and stage III. Patients with or without measurable disease may be included.
- Tumor expression of Melan-A by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis for patients of group I.
- Tumor expression of Melan-A and at least one of the tumor antigens MAGE-A10, NY-ESO-1, or LAGE-1 by rt-PCR analysis for patients of group II and III and for HLA-A2+ patients of groups IV and V. HLA-A2 negative patients of groups IV and V must only have NY-ESO-1 positive tumors to be eligible, while expression of Melan-A and MAGE-A10 is unimportant.
- If no frozen tissue is available, immunohistochemistry may be performed to detect tumor expression of Melan-A and NY-ESO-1.
- HLA-A2 positive (serological or molecular typing of Peripheral Blood Lymphocytes (PBL) for patients of groups 1 to 3. Patients of groups 4 and 5 may either be HLA-A2+ or HLA-A2-.
Key exclusion criteria (14 listed)
- Clinically significant heart disease (NYHA Class III or IV).
- Other serious illnesses, e.g., serious infections requiring antibiotics, uncontrolled peptic ulcer, or central nervous system disorders with major dysfunction.
- History of immunodeficiency disease or autoimmune disease.
- Known HIV positivity.
- Known seropositivity for hepatitis B surface antigen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Melan-A ELA + MontanideA maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months. | Biological | 1. Melan-A ELA |
| Melan-A ELA + NY-ESO-1b + MAGE-A10 + MontanideA maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months. | Biological | 2. Melan-A ELA + NY-ESO-1b + MAGE-A10 |
| Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpGA maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months. | Biological | 3. Melan-A ELA + NY-ESO-1b + MAGE-A10 + CpG |
| Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpGA maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months. | Biological | 4. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG |
| Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG+ IL-2A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months. | Biological | 5. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG+ IL-2 |
Primary outcome
Change From Baseline in Mean Number of Adverse Events (Serious and Non Serious Events)
Time frame: Change from baseline to end of Cycle 1 (3 months), end of Cycle 2 (8 months), end of Cycle 3 (13 months) and end of Boost Cycles (18 months to 23 months).
Safety of the vaccination was assessed according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) scale. The adverse events (AE) and serious adverse events (SAE) were registered at each study visit during the 3 vaccination cycles and boost cycles.
Fold Change From Baseline in ex Vivo Melan-A-specific CD8+ T Cells Frequency During the Vaccination Period
Time frame: Fold change from baseline in Melan-A-specific CD8+T-cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months).
Ex vivo frequency of Melan-A-specific CD8+ T cells was measured by multimer technique (tetramer assay) in a multicolor flow cytometry analysis. The fold change for each time point compared to baseline was calculated as: Melan-A-specific CD8+ T cell frequency at the time point/ Melan-A-specific CD8+ T cell frequency at baseline. Significant T cell response is defined by at least 2-fold change of Melan-A-specific CD8+ T cell frequency as compared to pre-immunotherapy.
Fold Change From Baseline in ex Vivo Frequency of Melan-A-specific IFN-γ-secreting CD8+ T Cells During the Vaccination Period
Time frame: Fold change from baseline in Melan-A-specific IFN-γ-secreting CD8+T-cells frequency at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Ex vivo frequency of Melan-A-specific CD8+ T cells producing IFN-γ (Interferon-gamma) was measured through the Enzyme-Linked Immunosorbent Spot (ELISpot) assay. The fold change for each time point compared to baseline was calculated as: Melan-A-specific IFN-γ-secreting CD8+ T cell frequency at the time point/ Melan-A-specific IFN-γ-secreting CD8+ T cell frequency at baseline.
Fold Change From Baseline in ex Vivo Frequency of NY-ESO-1-specific CD8+ T Cells During the Vaccination Period
Time frame: Fold change from baseline in NY-ESO-1-specific CD8+T-cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Ex vivo frequency of NY-ESO-1-specific CD8+ T cells was measured by multimer technique (tetramer assay) in a multicolor flow cytometry analysis. The fold change for each time point compared to baseline was calculated as: NY-ESO-1-specific CD8+ T cell frequency at the time point/ NY-ESO-1-specific CD8+ T cell frequency at baseline.
Fold Change From Baseline in ex Vivo Frequency of NY-ESO-1-specific IFN-γ-secreting CD8+ T Cells During the Vaccination Period
Time frame: Fold change from baseline in NY-ESO-1-specific IFN-γ-secreting CD8+T-cells frequency at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Ex vivo frequency of NY-ESO-1-specific CD8+ T cells producing IFN-γ (Interferon-gamma) was measured through the Enzyme-Linked Immunosorbent Spot (ELISpot) assay. The fold change for each time point compared to baseline was calculated as: NY-ESO-1-specific IFN-γ-secreting CD8+ T cell frequency at the time point/ NY-ESO-1-specific IFN-γ-secreting CD8+ T cell frequency at baseline.
Fold Change From Baseline in ex Vivo Frequency of MAGE-A10-specific CD8+ T Cells During the Vaccination Period
Time frame: Fold change from baseline in MAGE-A10-specific CD8+T-cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Ex vivo frequency of MAGE-A10-specific CD8+ T cells was measured by multimer technique (tetramer assay) in a multicolor flow cytometry analysis. The fold change for each time point compared to baseline was calculated as: MAGE-A10-specific CD8+ T cell frequency at the time point/ MAGE-A10-specific CD8+ T cell frequency at baseline.
Fold Change From Baseline in ex Vivo Frequency of MAGE-A10-specific IFN-γ-secreting CD8+ T Cells During the Vaccination Period
Time frame: Fold change from baseline in MAGE-A10-specific IFN-γ-secreting CD8+T-cells frequency at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
Ex vivo frequency of MAGE-A10-specific CD8+ T cells producing IFN-γ (Interferon-gamma) was measured through the Enzyme-Linked Immunosorbent Spot (ELISpot) assay. The fold change for each time point compared to baseline was calculated as: MAGE-A10-specific IFN-γ-secreting CD8+ T cell frequency at the time point/ MAGE-A10-specific IFN-γ-secreting CD8+ T cell frequency at baseline.
Percentage of in Vitro Stimulated NY-ESO-1 Lp-specific IFN-γ/TNF-α -Secreting CD4+ T Cells During the Vaccination Period
Time frame: Percentage of NY-ESO-1 lp-specific IFN-γ/TNF-α -secreting CD4+ T-cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
For each patient, total CD4+ T-cells were stimulated in the presence of peptide NY-ESO-1 long peptide (lp). After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged. The activation of NY-ESO-1 long peptide (lp)-specific CD4+ T cells were analyzed in vitro by Intracellular Cytokine Staining (ICS) via detection of IFN-γ (Interferon-gamma) and TNF-α (Tumor Necrosis Factor-alpha) producing cells.
Percentage of in Vitro Stimulated NY-ESO-1 Lp-specific IFN-γ/TNFα -Secreting CD8+ T Cells During the Vaccination Period
Time frame: Percentage of NY-ESO-1 lp-specific IFN-γ/TNF-α -secreting CD8+ T cells at the end of Cycle 1 (3 months), at the end of Cycle 2 (8 months), at the end of Cycle 3 (13 months) and if applicable at the end of Boost cycles (18 to 24 months)
For each patient, total CD8+ T cells were stimulated in the presence of peptide NY-ESO-1 long peptide (lp). After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged. The activation of NY-ESO-1 long peptide (lp)-specific CD8+ T cells were analyzed in vitro by Intracellular Cytokine Staining (ICS) via detection of IFN-γ (Interferon-gamma) and TNF-α (Tumor Necrosis Factor-alpha) producing cells.
1 secondary outcome
Disease Status Assessment During the Vaccination Period
Time frame: Disease status at baseline, after cycle 1 (3 months), after cycle 2 (8 months), after cycle 3 (13 months) and if applicable after boost cycles (16 months, 19 months or 22 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27853637Baumgaertner P, Costa Nunes C, Cachot A, Maby-El Hajjami H, Cagnon L, Braun M, Derre L, Rivals JP, Rimoldi D, Gnjatic S, Abed Maillard S, Marcos Mondejar P, Protti MP, Romano E, Michielin O, Romero P, Speiser DE, Jandus C. Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8+ and CD4+ T-cell responses with multiple specificities including a novel DR7-restricted epitope. Oncoimmunology. 2016 Sep 9;5(10):e1216290. doi: 10.1080/2162402X.2016.1216290. eCollection 2016.
- Results publication: PubMed 25808864Hebeisen M, Schmidt J, Guillaume P, Baumgaertner P, Speiser DE, Luescher I, Rufer N. Identification of Rare High-Avidity, Tumor-Reactive CD8+ T Cells by Monomeric TCR-Ligand Off-Rates Measurements on Living Cells. Cancer Res. 2015 May 15;75(10):1983-91. doi: 10.1158/0008-5472.CAN-14-3516. Epub 2015 Mar 25.
- Results publication: PubMed 25277238Bordry N, Costa-Nunes CM, Cagnon L, Gannon PO, Abed-Maillard S, Baumgaertner P, Murray T, Letovanec I, Lazor R, Bouchaab H, Rufer N, Romano E, Michielin O, Speiser DE. Pulmonary sarcoid-like granulomatosis after multiple vaccinations of a long-term surviving patient with metastatic melanoma. Cancer Immunol Res. 2014 Dec;2(12):1148-53. doi: 10.1158/2326-6066.CIR-14-0143. Epub 2014 Oct 2.
- Derived from this study: PubMed 31015344Costa-Nunes C, Cachot A, Bobisse S, Arnaud M, Genolet R, Baumgaertner P, Speiser DE, Sousa Alves PM, Sandoval F, Adotevi O, Reith W, Protti MP, Coukos G, Harari A, Romero P, Jandus C. High-throughput Screening of Human Tumor Antigen-specific CD4 T Cells, Including Neoantigen-reactive T Cells. Clin Cancer Res. 2019 Jul 15;25(14):4320-4331. doi: 10.1158/1078-0432.CCR-18-1356. Epub 2019 Apr 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier Michielin, MD PhD principal investigator
Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Melan-A ELA + Montanide, Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide and Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG in people with Melanoma, run by Centre Hospitalier Universitaire Vaudois at 2 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Mean Number of Adverse Events (Serious and Non Serious Events) (time frame: Change from baseline to end of Cycle 1 (3 months), end of Cycle 2 (8 months), end of Cycle 3 (13 months) and end of Boost Cycles (18 months to 23 months).). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00112242, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2020.