search
Back to results

Immunization of Disease-Free Melanoma Patients With Different HLA-A2 Peptides

Primary Purpose

Melanoma

Status
Terminated
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
Immunological peptides and immunological adjuvants
HLA-A2 peptides
Montanide ISA51
IMP321
Sponsored by
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring immunotherapy, adjuvants, IMP321, Montanide ISA51 VG, tumor-specific peptides

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically proven cutaneous melanoma. Patient's melanoma must be in one of the following AJCC stages : only primary tumor : T3b-T4, N0, M0. regional lymph node metastasis and/or in-transit metastasis, no distant metastasis (any T, N1-N3, M0) that has been removed. Any distant metastasis that has been removed (M1) HLA-A2 positive. Patients with previous regional metastatic disease must have one of their resected lesions analyzed by RT-PCR to determine expression of genes MAGE-1, MAGE-3, MAGE-4, MAGE-10, MAGE-C2, NA17, Tyrosinase or NY-ESO-1. However, expression of these genes by the tumor is not required to enter the study. Absence of detectable melanoma lesions. WHO/ECOG performance status of 1 or less (Karnofsky scale ≥ 70%). The following laboratory results: Hemoglobin ≥ 10 g/dl; Neutrophils ≥ 1,500/µl; Lymphocytes ≥ 700/µl; Platelets ≥ 100,000/µl; Serum creatinin ≤ 2.0 mg/dl; Serum bilirubin ≤ 2.0 mg/dl; LDH within normal institutional limits. 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, bleeding disorders, a second active malignancy, except basal cell carcinoma or in situ carcinoma of the uterine cervix. Active immunodeficiency disease or autoimmune disease. Positive serology for HIV (human immunodeficiency virus) or HCV (hepatitis C virus). Serum hepatitis B antigen (HBsAg) must be negative. More than one line of previous chemotherapy, or immunotherapy for the melanoma. Previous vaccination with one of the antigen present in the vaccine. Treatment with steroids or major immunosuppressive drugs within 4 weeks before study entry. 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.

Sites / Locations

  • Cliniques Universitaires Saint-Luc

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Group A

Group B

Group C

Group D

Arm Description

The eight HLA-A2 peptides

The eight HLA-A2 peptides + immunological adjuvant Montanide ISA51

the eight peptides HLA-A2 + IMP321

The eight HLA-A2 peptides + the 2 immunological adjuvants (Montanides ISA 51 and IMP321)

Outcomes

Primary Outcome Measures

Primary: Determination of the cytolytic T lymphocyte response in the different arms.; Toxicity of the combination peptide and immunological adjuvants

Secondary Outcome Measures

Secondary: Disease-free survival.

Full Information

First Posted
August 17, 2006
Last Updated
March 4, 2019
Sponsor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Collaborators
Immutep S.A.S.
search

1. Study Identification

Unique Protocol Identification Number
NCT00365937
Brief Title
Immunization of Disease-Free Melanoma Patients With Different HLA-A2 Peptides
Official Title
Immunization of Disease-Free Melanoma Patients With Different HLA-A2 Peptides
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
New regulatories of the peptides by the pharmaceutical company (the seller)
Study Start Date
August 2006 (Actual)
Primary Completion Date
December 13, 2013 (Actual)
Study Completion Date
December 13, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Collaborators
Immutep S.A.S.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Open-label single center study. Patients will be divided in four groups of 7. Group 1: 8 melanoma-specific peptides in saline; Group 2: same mix of peptides + Montanide ISA51; Group 3: same mix of peptides + IMP321 500 µg; Group 4: same mix of peptides + IMP321 500 µg + Montanide ISA51. These vaccines will be administered every 3 weeks on 5 occasions by intradermal and superficial subcutaneous injections.
Detailed Description
Open-label single center study. Patients will be divided in four groups of 7. The patients will be entered sequentially at the time they present in clinic, and randomized in one of the four groups. The first group of patients will receive a dose of 300 µg of each of the MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2, NA17.A2, Tyrosinase.A2 and NY-ESO-1.A2 peptides without adjuvant. The peptides will be mixed together and administered by intradermal and superficial subcutaneous injections at two sites every three weeks on 5 occasions (3 months). The second group of patients will receive on 5 occasions a vaccine containing the same 8 peptides mixed together but emulsified in 1 ml of Montanide ISA51. This vaccine will be also administered by intradermal and subcutaneous injections every three weeks. The third cohort of patients will receive at 3 weeks-interval on 5 occasions the mix of 8 peptides and 500 µg of IMP321. These two injections will be done at the same site, first adjuvant IMP321 then the peptides. The last seven patients will receive as vaccine the same mix of peptides emulsified with Montanide ISA 51 VG and IMP321 injected with the same procedure as cohort 3. These vaccines will be administrated every 3 weeks on 5 occasions by intradermal and superficial subcutaneous injections. Blood samples will be obtained from a buffy-coat at weeks 1 and 16. PBL collected at baseline (day 1) and at week 16 will be tested to determine whether a specific CTL response, defined as a 10-times or more increase in CTL frequency, occurred. For the patients with an anti-vaccine lymphocyte response, 100 ml of blood will be collected every three months in order to monitor their immune response. If a decrease in CTL frequency by a factor 10 is observed, the patients will be revaccinated three times at three weeks interval with the peptide(s) against which he developed an immune response mixed with the adjuvant he already received. The disease status will be assessed at study entry and thereafter every 3 months during one year. At any time, relapse will result in withdrawal of the patient from the trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
immunotherapy, adjuvants, IMP321, Montanide ISA51 VG, tumor-specific peptides

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Description
The eight HLA-A2 peptides
Arm Title
Group B
Arm Type
Experimental
Arm Description
The eight HLA-A2 peptides + immunological adjuvant Montanide ISA51
Arm Title
Group C
Arm Type
Experimental
Arm Description
the eight peptides HLA-A2 + IMP321
Arm Title
Group D
Arm Type
Experimental
Arm Description
The eight HLA-A2 peptides + the 2 immunological adjuvants (Montanides ISA 51 and IMP321)
Intervention Type
Biological
Intervention Name(s)
Immunological peptides and immunological adjuvants
Intervention Type
Biological
Intervention Name(s)
HLA-A2 peptides
Intervention Description
Tyrosinase.A2: lyophilized powder, 326 mcg, 5 injections every 3 weeks MAGE-C2.A2: lyophilized powder, 320 mcg, 5 injections every 3 weeks NY-ESO-1b.A2: lyophilized powder, 290 mcg, 5 injections every 3 weeks MAGE-4.A2: lyophilized powder, 299 mcg, 5 injections every 3 weeks MAGE-3.A2: lyophilized powder, 300 mcg, 5 injections every 3 weeks MAGE-1.A2: lyophilized powder, 298 mcg, 5 injections every 3 weeks NA17.A2 (GnTV): lyophilized powder, 300 mcg, 5 injections every 3 weeks MAGE-10.A2: lyophilized powder, 309 mcg, 5 injections every 3 weeks
Intervention Type
Biological
Intervention Name(s)
Montanide ISA51
Intervention Description
Oil emulsion (W/O: droplet test S57 IN 001), conductivity less than 10mcs.cm-1, viscosity: 1500 mPas (brookfield DVI - spindle 2- Speed 30). For human applications. Injected 5 times every 3 weeks.
Intervention Type
Biological
Intervention Name(s)
IMP321
Intervention Description
Official name of the LAG-3 molecule is CD223. Chemical structure: hLAG-3Ig is a soluble human recombinant LAG-3 protein comprising the extra-cellular Ig-like domains. The IMP321 drug product is composed of a soluble recombinant protein at a 1.18 mg/ml concentration, in PBS (Na2HPO4 2H2O 8.1mM, KH2PO4 1.47mM, NaCl 137mM, KCl 2.68mM, PH 7.2). Batch number: S017/LC1/041011.IMP321 will be provided in 250mcl aliquots in brosilicate siliconized vials.
Primary Outcome Measure Information:
Title
Primary: Determination of the cytolytic T lymphocyte response in the different arms.; Toxicity of the combination peptide and immunological adjuvants
Secondary Outcome Measure Information:
Title
Secondary: Disease-free survival.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically proven cutaneous melanoma. Patient's melanoma must be in one of the following AJCC stages : only primary tumor : T3b-T4, N0, M0. regional lymph node metastasis and/or in-transit metastasis, no distant metastasis (any T, N1-N3, M0) that has been removed. Any distant metastasis that has been removed (M1) HLA-A2 positive. Patients with previous regional metastatic disease must have one of their resected lesions analyzed by RT-PCR to determine expression of genes MAGE-1, MAGE-3, MAGE-4, MAGE-10, MAGE-C2, NA17, Tyrosinase or NY-ESO-1. However, expression of these genes by the tumor is not required to enter the study. Absence of detectable melanoma lesions. WHO/ECOG performance status of 1 or less (Karnofsky scale ≥ 70%). The following laboratory results: Hemoglobin ≥ 10 g/dl; Neutrophils ≥ 1,500/µl; Lymphocytes ≥ 700/µl; Platelets ≥ 100,000/µl; Serum creatinin ≤ 2.0 mg/dl; Serum bilirubin ≤ 2.0 mg/dl; LDH within normal institutional limits. 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, bleeding disorders, a second active malignancy, except basal cell carcinoma or in situ carcinoma of the uterine cervix. Active immunodeficiency disease or autoimmune disease. Positive serology for HIV (human immunodeficiency virus) or HCV (hepatitis C virus). Serum hepatitis B antigen (HBsAg) must be negative. More than one line of previous chemotherapy, or immunotherapy for the melanoma. Previous vaccination with one of the antigen present in the vaccine. Treatment with steroids or major immunosuppressive drugs within 4 weeks before study entry. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-François Baurain, M.D, PhD
Organizational Affiliation
Cliniques universitaires Saint-Luc
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium

12. IPD Sharing Statement

Learn more about this trial

Immunization of Disease-Free Melanoma Patients With Different HLA-A2 Peptides

We'll reach out to this number within 24 hrs