MelanomaPhase 1/2LAG-3/IMP321NCT01308294

Immunotherapy of HLA-A2 Positive Stage II-IV Melanoma Patients

A Phase 1/2 study testing 2 vaccine injections in 1 limb, 2 vaccine injections in distinct limbs and 2 "vaccine injections" in distinct limbs in people with Melanoma, run by Centre Hospitalier Universitaire Vaudois at 1 site in Switzerland.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Melanoma
What is being tested?: 2 vaccine injections in 1 limb, 2 vaccine injections in distinct limbs and 2 "vaccine injections" in distinct limbs
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteSwitzerland
Study dates: Jun 2010to Apr 2014
Phase: Phase 1/2
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 II, III or IV melanoma patients.
Tumor expression of Melan-A.
Human leukocyte antigen-A2 (HLA-A2) positive.
Expected survival of at list 3 months.
Karnofsky scale performance status of 70 % or more.
Age ≥ 18 years.

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

Who cannot join

Clinically significant heart disease.
Serious illness, eg. serious infections requiring antibiotics, uncontrolled peptic ulcer, or central nervous system disorders.
History of immunodeficiency disease or autoimmune disease.
Metastatic disease to the central nervous system, unless treated and stable.
Known HIV positivity.
Known seropositivity for hepatitis B surface antigen.

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Concomitant treatment with steroids, antihistamine drugs. Topical or inhalation steroids are permitted.
Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
Pregnancy or lactation.
Women of childbearing potential not using a medically acceptable means of contraception.
Psychiatric or addictive disorders that may compromise the ability to give informed consent.
Lack of availability of the patient for immunological and clinical follow-up assessment.
Coagulation or bleeding disorders.
Kidney dysfunction with creatinine > 2 X the upper limit of the normal value.
Reported strong (allergic) reactions to previous vaccination.

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

Oncology Department, CHUV
Lausanne, Canton of Vaud, 1011

Other trials in Switzerland

About this study

Official title: Vaccination of Melanoma Patients (Stage II-IV) With ImmuFact IMP321, Tumor Antigenic Peptides and Montanide

Read the detailed description

The primary objective of this study is:

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

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

Conditions: Melanoma
Being tested: 2 vaccine injections in 1 limb, 2 vaccine injections in distinct limbs, 2 "vaccine injections" in distinct limbs
Keywords: Melanoma, Stage II-IV, Immunotherapy, Vaccination, HLA class I and II tumor-specific peptides, IMP321, Montanide ISA-51
Medical subject headings: Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

2 vaccine injections in 1 limbBiological
Also called vaccine1: NY-ESO-1,MAGE-3.A2, NA-17, IMP321, Montanide, vaccine 2: Melan-A, MAGE-A3-DP4 , IMP321, Montanide
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.
2 vaccine injections in distinct limbsBiological
Also called vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17,IMP321, Montanide, vaccine 2: Melan-A, MAGE-A3-DP4, IMP321, Montanide)
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 limbsBiological
Also called vaccine 1: NY-ESO-1, NA-17, IMP321, Montanide, vaccine 2: Melan-A, NA-17, IMP321, Montanide

Study groups in NCT01308294
Study group	Role	What they receive
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) Receives: Biological: 2 vaccine injections in 1 limb
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) Receives: Biological: 2 vaccine injections in distinct limbs
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) Receives: Biological: 2 "vaccine injections" in distinct limbs

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: In vitro stimulated NY-EYO-1 specific CD8+ T cells were measured in PBMC collected at the end of Cycle 1 (Week 7), end of Cycle 2 (Week 25), end of Cycle 3 (Week 40), and Follow-up (6 to 18 months after the end of Cycle 3).

Secondary outcomes (1)

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 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.
- Progressive 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: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2010Apr 2014

First posted4 Mar 2011 (estimated)
Study startJun 2010
Primary completionApr 2014
Study completionApr 2014

Why it stopped: Low enrollment rate

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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: open label, non comparative study in patients suffering from stage II, III or IV melanoma
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01308294
Sponsor's protocol ID: P009-2010DR1082
Acronym: LAG-3/IMP321
Status last verified: May 2020
First submitted: 3 Mar 2011
Last updated: 11 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 21142803
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.
PubMed 19755389
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.
PubMed 20413326
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.
PubMed 26500235

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Melanoma trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Vaccination of Melanoma Patients (Stage II-IV) With ImmuFact IMP321, Tumor Antigenic Peptides and Montanide
ClinicalTrials.gov ID: NCT01308294
Acronym / sponsor ID: LAG-3/IMP321 / P009-2010DR1082
Conditions: Melanoma
Keywords: Melanoma, Stage II-IV, Immunotherapy, Vaccination, HLA class I and II tumor-specific peptides, IMP321, Montanide ISA-51
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Low enrollment rate
Enrolment: 16 participants (actual)
Lead sponsor: Centre Hospitalier Universitaire VaudoisUniversity, hospital or other
Collaborators: Immutep S.A.S.
Study start: Jun 2010 (actual)
Primary completion: Apr 2014 (actual)
Study completion: Apr 2014 (actual)
First posted: 4 Mar 2011 (estimated)
Results: Posted 20 Mar 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The primary objective of this study is:

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

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

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: open label, non comparative study in patients suffering from stage II, III or IV melanoma

Arm	Type	Receives
2 vaccine injections in 1 limb	Experimental	Biological: 2 vaccine injections in 1 limb9 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	Biological: 2 vaccine injections in distinct limbsGroupe2: 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	Biological: 2 "vaccine injections" in distinct limbsGroupe3: 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)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Histologically confirmed stage II, III or IV melanoma patients.
Tumor expression of Melan-A.
Human leukocyte antigen-A2 (HLA-A2) positive.
Expected survival of at list 3 months.
Karnofsky scale performance status of 70 % or more.

Key exclusion criteria (15 listed)

Clinically significant heart disease.
Serious illness, eg. serious infections requiring antibiotics, uncontrolled peptic ulcer, or central nervous system disorders.
History of immunodeficiency disease or autoimmune disease.
Metastatic disease to the central nervous system, unless treated and stable.
Known HIV positivity.

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
2 vaccine injections in 1 limbAlso: vaccine1: NY-ESO-1,MAGE-3.A2, NA-17, IMP321, Montanide, vaccine 2: Melan-A, MAGE-A3-DP4 , IMP321, MontanideParticipants 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.	Biological	2 vaccine injections in 1 limb
2 vaccine injections in distinct limbsAlso: vaccine 1: NY-ESO-1, MAGE-3.A2, NA-17,IMP321, Montanide, vaccine 2: Melan-A, MAGE-A3-DP4, IMP321, Montanide)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.	Biological	2 vaccine injections in distinct limbs
2 "vaccine injections" in distinct limbsAlso: vaccine 1: NY-ESO-1, NA-17, IMP321, Montanide, vaccine 2: Melan-A, NA-17, IMP321, Montanide	Biological	2 "vaccine injections" in distinct limbs

Primary outcome

Ex Vivo Frequency of Melan-A Specific CD8+T Cells
Time frame: 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).
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.
In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Interferon-gamma (IFN-γ)
Time frame: 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).
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.
In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Tumor Necrosis Factor-alpha (TNF-α)
Time frame: 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).
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.
In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells
Time frame: 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).
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.
In Vitro Frequency of Melan-A-specific CD8+T Cells After Stimulation
Time frame: 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).
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 Frequency of NY-ESO-1-specific CD8+ T Cells
Time frame: 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).
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.

1 secondary outcome

Tumor Response
Time frame: 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)

Results and safety

Results posted to the registry on 20 Mar 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1	10	10
Group 2	6	6
Group 3	0	0

Primary outcome: Ex Vivo Frequency of Melan-A Specific CD8+T Cells

Time frame: 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).. Median (Standard Deviation). Unit: Fold change of % Melan-A CD8+T ex vivo

Measure	Group 1 n = 10	Group 2 n = 6	Group 3 n = 0
End cycle 1	1.21 (0.47)	1.25 (1.44)	–
End cycle 2	1.09 (18.21)	1.67 (2.14)	–
End cycle 3	0.91 (5.77)	1.83 (1.79)	–
Follow up	1.00 (2.14)	0.28 (0.39)	–
Max	1.21 (18.21)	1.83 (2.14)	–

Population analysed: No patients were included in the group 3

Primary outcome: In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Interferon-gamma (IFN-γ)

Time frame: 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).. Median (Standard Deviation). Unit: % MAGE-A3.DP4 specific CD4+T IFN-γ

Measure	Group 1 n = 10	Group 2 n = 6	Group 3 n = 0
Baseline	0 (0)	0 (0)	–
End of cycle 1	0.47 (1.05)	1.89 (2.23)	–
End of cycle 2	1.11 (1.06)	1.63 (1.60)	–
End of cycle 3	2.00 (1.74)	0.29 (0.91)	–
Follow up	1.46 (1.97)	0.77 (0.91)	–

Population analysed: No patients were included in the group 3

Primary outcome: In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells Producing Tumor Necrosis Factor-alpha (TNF-α)

Time frame: 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).. Mean (Standard Deviation). Unit: % MAGE A3.DP4 specific CD4+T TNFα

Measure	Group 1 n = 10	Group 2 n = 6	Group 3 n = 0
Baseline	0.01 (0.01)	0 (0)	–
End of cycle 1	0.70 (2.33)	3.39 (2.35)	–
End of cycle 2	1.05 (2.74)	2.31 (2.04)	–
End of cycle 3	1.63 (3.90)	0.60 (0.80)	–
Follow up	2.04 (1.57)	3.63 (3.06)	–

Population analysed: No patients were included in the group 3

Primary outcome: In Vitro Frequency of MAGE A3.DP4-specific CD4+ T Cells

Time frame: 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).. Median (Standard Deviation). Unit: Fold change of % MageA3.DP4 CD4+T

Measure	Group 1 n = 10	Group 2 n = 6	Group 3 n = 0
End cycle 1	0.19 (2.02)	0.22 (0.17)	–
End of cycle 2	0.88 (1.79)	1.97 (1.77)	–
End of cycle 3	1.57 (1.64)	0.66 (0.61)	–
Follow up	0.63 (2.63)	0.62 (0.32)	–
Max	1.96 (2.67)	1.28 (1.69)	–

Population analysed: No patients were included in group 3

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1	1 of 10 (10%)	10 of 10 (100%)	0 of 10
Group 2	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Group 3	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): Early termination leading to small numbers of subjects analyzed

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21142803Sierro 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.
Background: PubMed 19755389Brignone 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.
Background: PubMed 20413326Speiser 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.
Results publication: PubMed 26500235Legat 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.
Multidisciplinary Oncology Center, CHUV, LausanneLink provided by the sponsor.

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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

Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 9 inclusion and 15 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: stopped early, as of the sponsor's last update on 11 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 1 site 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 20 Mar 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?

Ex Vivo Frequency of Melan-A Specific CD8+T Cells (time frame: 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).). The study lists 6 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 NCT01308294, 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 11 Jun 2020.