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Low enrollment rate
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| Name | Class |
|---|---|
| Immutep S.A.S. | INDUSTRY |
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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.
The primary objective of this study is:
The secondary objective is to document tumor responses in patients following this vaccination.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2 vaccine injections in 1 limb | Experimental | 9 patients initially planned: patients received peptides with IMP321/LAG-3Ig and Montanide in 2 injections sites at 5 cm distance from each other 2 vaccine injections in same limb (vaccine 1 : NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2 : Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) |
|
| 2 vaccine injections in distinct limbs | Experimental | Groupe2: 2 vaccine injections in different limb should include 9 patients that were initially planned: patients received the same vaccine in 2 syringes injected each in a distinct limb (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) |
|
| 2 "vaccine injections" in distinct limbs | Experimental | Groupe3: 2 vaccine injections in distinct limb should include 9 patients that were initially planned; due to premature trial termination, no patients could be enrolled. Patients of this group should have received the same vaccine but without the MHC class II peptide (MAGE-A3) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 2 vaccine injections in 1 limb | Biological | Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in the same limb at about 5 cm distance from each other. |
| Measure | Description | Time Frame |
|---|---|---|
| Ex Vivo Frequency of Melan-A Specific CD8+T Cells | Cellular immunity was evaluated through the activation and the expansion of Melan-A-specific CD8+ cytotoxic T lymphocytes. Their frequency was measured in the peripheral blood mononuclear cells (PBMC) directly ex vivo (i.e. without prior in vitro expansion) by multicolor flow cytometry with Melan-A ELA tetramers. 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. | 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). |
| In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Interferon-gamma (IFN-γ) | The activation of peptide-specific CD4+ T cells was analyzed in vitro before and after vaccination by Intracellular Cytokine Staining (ICS). From each patient, total CD4+ T-cells were stimulated in the presence of peptide MAGE-A3.DP4 LP (MAGE-A3243-258 peptide presented by autologous cells). After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged. Specific CD4+ T cells responses were identified via detection of IFN-γ producing cells. | 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). |
| In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Tumor Necrosis Factor-alpha (TNF-α) | The activation of peptide-specific CD4+ T cells was analyzed in vitro before and after vaccination by ICS. From each patient, total CD4+ T-cells were stimulated in the presence of peptide MAGE-A3.DP4 LP (MAGE-A3243-258 peptide presented by autologous cells). After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged. Specific CD4+ T cells responses were identified via detection of TNF-α producing cells. |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Response | The assessment of the baseline disease status was performed, using CT (Computed Tomography) scan or PET (Positron Emission Tomography)/ CT scan, at screening visit or within 8 weeks preceding the screening visit. Imagery examinations occurred after the end of each vaccination cycle. The tumor response was assessed according to the classification World Health Organization (WHO) 1979 and defined as:
|
Not provided
Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Olivier Michielin, MD PhD | Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Oncology Department, CHUV | Lausanne | Canton of Vaud | 1011 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21142803 | Background | 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. | |
| 19755389 | Background | 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. |
| Label | URL |
|---|---|
| Multidisciplinary Oncology Center, CHUV, Lausanne | View source |
Not provided
An unexplained high percentage, i.e. about 90% of the 11 prescreened patients were HLA-A2 negative. We assume that this was due to the increasing ethnic diversity of patients.
The consequence of the time delay was that some of the peptides expired definitively.
16 patients were selected between June 15, 2010 and January 24, 2013. Among them 10 patients were included in the group 1 and 6 in the group 2. Since January 2013, 11 patients have been prescreened but could not be included in the study. On April 15, 2014, the decision had to taken to abort the study (16 patients included, while 28 were planned).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Group 1 | 2 vaccine injections in same limb (vaccine 1 : NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2 : Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) 2 vaccine injections in 1 limb: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in the same limb at about 5 cm distance from each other. |
| FG001 | Group 2 | 2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) 2 vaccine injections in different limbs: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide.The content of each syringe is injected s.c. in different limbs. |
| FG002 | Group 3 | 2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A peptide + IMP321 + Montanide) 2 vaccine injections in different limbs, the vaccine does not contain the MHC class II peptide MAGE-A3-DP4: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A peptide with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in different limbs. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 |
| |||||||||||||
| Cycle 2 |
| |||||||||||||
| Cycle 3 |
|
Due to premature trial termination, no patients could be enrolled in the Group 3.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Group 1: 2 Vaccine Injections in 1 Limb | 9 patients initially planned: patients received peptides with IMP321/LAG-3Ig and Montanide in 2 injections sites at 5 cm distance from each other 2 vaccine injections in same limb (vaccine 1 : NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide)(vaccine 2 : Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) 2 vaccine injections in 1 limb: Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in the same limb at about 5 cm distance from each other. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ex Vivo Frequency of Melan-A Specific CD8+T Cells | Cellular immunity was evaluated through the activation and the expansion of Melan-A-specific CD8+ cytotoxic T lymphocytes. Their frequency was measured in the peripheral blood mononuclear cells (PBMC) directly ex vivo (i.e. without prior in vitro expansion) by multicolor flow cytometry with Melan-A ELA tetramers. 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. | No patients were included in the group 3 | Posted | Median | Standard Deviation | Fold change of % Melan-A CD8+T ex vivo | 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). |
|
All adverse events were recorded from the first vaccination visit (Day 0) to the last vaccination visit (V9) of the cycle 3 of vaccination (week 39) therefore the adverse events were collected for 9 months.
No patients were included in the group 3. All adverse events were collected irrespective of their frequency, their severity and relationship to the study drug.
The adverse events that were expected, according to the Investigator's Brochure of the different vaccine components, were assessed systematically at each visit study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1 | 2 vaccine injections in same limb (vaccine 1 : NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2 : Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) 2 vaccine injections in 1 limb: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in the same limb at about 5 cm distance from each other. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper limb fracture | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
Early termination leading to small numbers of subjects analyzed
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Olivier Michielin, MD PhD | Department of Oncology, Division of Medical Oncology University Hospital Lausanne | +41 21 314 01 85 | Olivier.Michielin@chuv.ch |
Not provided
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided
| ID | Term |
|---|---|
| C000720328 | soluble LAG-3 protein, human |
| C000712049 | Monatide (IMS 3015) |
Not provided
Not provided
Not provided
open label, non comparative study in patients suffering from stage II, III or IV melanoma
Not provided
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Not provided
Not provided
|
|
| 2 vaccine injections in distinct limbs | Biological | Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide.The content of each syringe is injected s.c. in different limbs. |
|
|
| 2 "vaccine injections" in distinct limbs | Biological |
|
|
| 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). |
| In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells | Frequencies of specific MAGE-A3.DP4-specific CD4+ T cells were quantified by flow cytometry using class II tetramers after 10 days of in vitro stimulation. The fold change for each time point compared to baseline was calculated as: MAGE-A3.DP4-specific CD4+ T cell frequency at the time point/ MAGE-A3.DP4-specific CD4+ T cell frequency at baseline. | 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). |
| In Vitro Frequency of Melan-A-specific CD8+T Cells After Stimulation | After 12 days of in vitro stimulation with Melan-A peptides, CD8+ T cells were analyzed by flow cytometry using tetramer staining. 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. | 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). |
| In Vitro Frequency of NY-ESO-1-specific CD8+ T Cells | After 12 days of in vitro stimulation with NY-ESO-1 peptide, CD8+ T cells were analyzed by flow cytometry using tetramer staining. 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. | 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). |
| 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) |
| 20413326 | Background | 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. |
| 26500235 | Result | 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. |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | Group 2: 2 Injections in Different Limbs | 9 patients initially planned: patients received the same vaccine in 2 syringes injected each in a distinct limb 2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) 2 vaccine injections in different limbs: Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide.The content of each syringe is injected s.c. in different limbs. |
| BG002 | Group 3: 2 Injections in Different Limbs | 9 patients initially planned: due to premature trial termination, no patients could be enrolled in this last group. 2 vaccine injections in different limbs; patients of this group should have received the same vaccine but without the MHC class II peptide (MAGE-A3 LP) in 2 syringes injected each in a distinct limb. 2 vaccine injections without MHC class II peptide in different limbs: Participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A peptide with IMP321/LAG-3 ± Montanide. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Group 1 |
2 vaccine injections in same limb (vaccine 1 : NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2 : Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) 2 vaccine injections in 1 limb: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in the same limb at about 5 cm distance from each other. |
| OG001 | Group 2 | 2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) 2 vaccine injections in different limbs: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide.The content of each syringe is injected s.c. in different limbs. |
| OG002 | Group 3 | 2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A peptide + IMP321 + Montanide) 2 vaccine injections in different limbs, the vaccine does not contain the MHC class II peptide MAGE-A3-DP4: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A peptide with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in different limbs. |
|
|
| Primary | In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Interferon-gamma (IFN-γ) | The activation of peptide-specific CD4+ T cells was analyzed in vitro before and after vaccination by Intracellular Cytokine Staining (ICS). From each patient, total CD4+ T-cells were stimulated in the presence of peptide MAGE-A3.DP4 LP (MAGE-A3243-258 peptide presented by autologous cells). After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged. Specific CD4+ T cells responses were identified via detection of IFN-γ producing cells. | No patients were included in the group 3 | Posted | Median | Standard Deviation | % MAGE-A3.DP4 specific CD4+T IFN-γ | 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). |
|
|
|
| Primary | In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Tumor Necrosis Factor-alpha (TNF-α) | The activation of peptide-specific CD4+ T cells was analyzed in vitro before and after vaccination by ICS. From each patient, total CD4+ T-cells were stimulated in the presence of peptide MAGE-A3.DP4 LP (MAGE-A3243-258 peptide presented by autologous cells). After 10 days, cell cultures were challenged for 4h with the peptide or left unchallenged. Specific CD4+ T cells responses were identified via detection of TNF-α producing cells. | No patients were included in the group 3 | Posted | Mean | Standard Deviation | % MAGE A3.DP4 specific CD4+T TNFα | 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). |
|
|
|
| Primary | In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells | Frequencies of specific MAGE-A3.DP4-specific CD4+ T cells were quantified by flow cytometry using class II tetramers after 10 days of in vitro stimulation. The fold change for each time point compared to baseline was calculated as: MAGE-A3.DP4-specific CD4+ T cell frequency at the time point/ MAGE-A3.DP4-specific CD4+ T cell frequency at baseline. | No patients were included in group 3 | Posted | Median | Standard Deviation | Fold change of % MageA3.DP4 CD4+T | 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). |
|
|
|
| Primary | In Vitro Frequency of Melan-A-specific CD8+T Cells After Stimulation | After 12 days of in vitro stimulation with Melan-A peptides, CD8+ T cells were analyzed by flow cytometry using tetramer staining. 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. | No patients were included in group 3 | Posted | Median | Standard Deviation | Fold change of % Melan-A CD8+T cells | 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). |
|
|
|
| Primary | In Vitro Frequency of NY-ESO-1-specific CD8+ T Cells | After 12 days of in vitro stimulation with NY-ESO-1 peptide, CD8+ T cells were analyzed by flow cytometry using tetramer staining. 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. | No patients were included in the group 3 | Posted | Median | Standard Deviation | Fold change of % NY-ESO-1 CD8+T cells | 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 | Tumor Response | The assessment of the baseline disease status was performed, using CT (Computed Tomography) scan or PET (Positron Emission Tomography)/ CT scan, at screening visit or within 8 weeks preceding the screening visit. Imagery examinations occurred after the end of each vaccination cycle. The tumor response was assessed according to the classification World Health Organization (WHO) 1979 and defined as:
| No patients were included in the group 3 | Posted | Count of Participants | Participants | 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) |
|
|
|
| 0 |
| 10 |
| 1 |
| 10 |
| 10 |
| 10 |
| EG001 | Group 2 | 2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A, MAGE-A3-DP4 peptides + IMP321 + Montanide) 2 vaccine injections in different limbs: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A and MAGE-A3-DP4 peptides with IMP321/LAG-3 ± Montanide.The content of each syringe is injected s.c. in different limbs. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Group 3 | 2 vaccine injections in different limbs (vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17 peptides + IMP321 + Montanide) (vaccine 2: Melan-A peptide + IMP321 + Montanide) 2 vaccine injections in different limbs, the vaccine does not contain the MHC class II peptide MAGE-A3-DP4: All participants receive the vaccine separated in 2 syringes with syringe 1 containing NA-17, MAGE-3.A2 and NY-ESO-1 peptides with IMP321/LAG3 ± Montanide, and syringe 2 containing Melan-A peptide with IMP321/LAG-3 ± Montanide. The content of each syringe is injected s.c. in different limbs. | 0 | 0 | 0 | 0 | 0 | 0 |
| Lymphadenopathy inguinal | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Lymphoedema | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Haematoma | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Diabetes mellitus | Endocrine disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Eya lesions | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Aphtous stomatitis | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Inguinal hernia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Contusion | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hot flush | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hyperhidrosis | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Injection site haematoma | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Injection site pruritus | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oedema | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Performance status decreased | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Previous studies injection site induration | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hepatic pain | Hepatobiliary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Herpes Zoster | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Infected lymphocele | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Scar | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Skin injury | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Blood thyroid stimulating hormone increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Increased lactade dehydrogenase | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Karnofsky scale worsened | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Lymphocytes count decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Platelet count increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Positron emission abnormal | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Urine leucocytes esterase | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Abnormal weight gain | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pain in extermity | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Upper limb fracture | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Malignat melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Metastatic malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Metastases to skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Sinus polyps | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Coordination abnormal | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dizzines | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Head discomfort | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Cystitis/Dysuria | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hematuria | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Stress urinary incontinence | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Balanitis | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Menauposal symptoms | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Menstruation delayed | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Bronchitis haemophilus | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Chest pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dysponea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hoarsness of voice | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Musculoskeletal chest pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Rhinitis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Capilaritis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Erythema eyelid | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Granuloma skin | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Puritus | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pruritus generalized | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Subcutaneous nodules | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA (15.1) | Systematic Assessment |
|
| Injection site induration | General disorders | MedDRA (15.1) | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (15.1) | Systematic Assessment |
|
| Injection site recall reaction | General disorders | MedDRA (15.1) | Systematic Assessment |
|
| Injection site warmth | General disorders | MedDRA (15.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (15.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (15.1) | Systematic Assessment |
|
| Fever | General disorders | MedDRA (15.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
|
| Influenza like illness | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (15.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| End of cycle 2 |
|
| End of cycle 3 |
|
| Follow up |
|
| End of cycle 2 |
|
| End of cycle 3 |
|
| Follow up |
|
| End of cycle 3 |
|
| Follow up |
|
| Max |
|
| End cycle 3 |
|
| Follow up |
|
| Max |
|
| End cycle 3 |
|
| Follow up |
|
| Max |
|
| SD |
|
| PD |
|
| Disease status at cycle 2 end |
|
|
| Disease status at cycle 3 end |
|
|