Back to resultsImmunotherapy of Stage III/IV Melanoma Patients
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
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
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Immunotherapy, Vaccination, Melanoma, Melan-A/Mart-1 peptide, MAGE-A10 peptide, NY-ESO-1 peptide, Montanide, CpG
Eligibility Criteria
Inclusion Criteria: 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. 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. Exclusion Criteria: 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). 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.
Sites / Locations
- Oncology Department, Lausanne University Hospital (CHUV) and University of Lausanne
- Division of Oncology at the Geneva University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
1. Melan-A ELA
2. Melan-A ELA + NY-ESO-1b + MAGE-A10
3. Melan-A ELA + NY-ESO-1b + MAGE-A10 + CpG
4. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG
5. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG+ IL-2
Arm Description
500 mcg Melan-A ELA analog peptide + 1 ml Montanide ISA-51
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
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
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
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
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT00112242
First Posted
May 31, 2005
Last Updated
June 2, 2020
Sponsor
Centre Hospitalier Universitaire Vaudois
Collaborators
Ludwig Institute for Cancer Research
1. Study Identification
Unique Protocol Identification Number
NCT00112242
Brief Title
Immunotherapy of Stage III/IV Melanoma Patients
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre Hospitalier Universitaire Vaudois
Collaborators
Ludwig Institute for Cancer Research
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Immunotherapy, Vaccination, Melanoma, Melan-A/Mart-1 peptide, MAGE-A10 peptide, NY-ESO-1 peptide, Montanide, CpG
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1. Melan-A ELA
Arm Type
Experimental
Arm Description
500 mcg Melan-A ELA analog peptide + 1 ml Montanide ISA-51
Arm Title
2. Melan-A ELA + NY-ESO-1b + MAGE-A10
Arm Type
Experimental
Arm Description
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
Arm Title
3. Melan-A ELA + NY-ESO-1b + MAGE-A10 + CpG
Arm Type
Experimental
Arm Description
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
Arm Title
4. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG
Arm Type
Experimental
Arm Description
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
Arm Title
5. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG+ IL-2
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Melan-A ELA + Montanide
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG+ IL-2
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in Mean Number of Adverse Events (Serious and Non Serious Events)
Description
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.
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).
Title
Fold Change From Baseline in ex Vivo Melan-A-specific CD8+ T Cells Frequency During the Vaccination Period
Description
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.
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).
Title
Fold Change From Baseline in ex Vivo Frequency of Melan-A-specific IFN-γ-secreting CD8+ T Cells During the Vaccination Period
Description
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.
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)
Title
Fold Change From Baseline in ex Vivo Frequency of NY-ESO-1-specific CD8+ T Cells During the Vaccination Period
Description
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.
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)
Title
Fold Change From Baseline in ex Vivo Frequency of NY-ESO-1-specific IFN-γ-secreting CD8+ T Cells During the Vaccination Period
Description
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.
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)
Title
Fold Change From Baseline in ex Vivo Frequency of MAGE-A10-specific CD8+ T Cells During the Vaccination Period
Description
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.
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)
Title
Fold Change From Baseline in ex Vivo Frequency of MAGE-A10-specific IFN-γ-secreting CD8+ T Cells During the Vaccination Period
Description
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.
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)
Title
Percentage of in Vitro Stimulated NY-ESO-1 Lp-specific IFN-γ/TNF-α -Secreting CD4+ T Cells During the Vaccination Period
Description
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.
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)
Title
Percentage of in Vitro Stimulated NY-ESO-1 Lp-specific IFN-γ/TNFα -Secreting CD8+ T Cells During the Vaccination Period
Description
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.
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)
Secondary Outcome Measure Information:
Title
Disease Status Assessment During the Vaccination Period
Description
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.
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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.
Exclusion Criteria:
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).
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Michielin, MD PhD
Organizational Affiliation
Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oncology Department, Lausanne University Hospital (CHUV) and University of Lausanne
City
Lausanne
State/Province
Vaud
ZIP/Postal Code
1011
Country
Switzerland
Facility Name
Division of Oncology at the Geneva University Hospital
City
Geneva
ZIP/Postal Code
1211
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
27853637
Citation
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.
Results Reference
result
PubMed Identifier
25808864
Citation
Hebeisen 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 Reference
result
PubMed Identifier
25277238
Citation
Bordry 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.
Results Reference
result
PubMed Identifier
31015344
Citation
Costa-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.
Results Reference
derived
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Immunotherapy of Stage III/IV Melanoma Patients
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