- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00145145
Immunization With the MAGE-3.A1 Peptide Mixed With the Adjuvant CpG 7909 in Patients With Metastatic Melanoma
Phase I/II Study of Immunization With the MAGE-3.A1 Peptide Mixed With the Immunological Adjuvant CpG 7909 in Patients With Metastatic Melanoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients will be vaccinated every two weeks on six occasions. On each vaccination day, the MAGE-3.A1 peptide (300 µg) mixed with CpG 7909 (5 mg) will be administered twice intradermally (10% of the dose each) and twice subcutaneously (40% of the dose each) in the arms and thighs.
Tumor staging will be performed before inclusion and at week 13. PBL collections will be performed before starting the treatment, and at weeks 3, 7 and 13. They will provide the T lymphocytes for the immunological analysis.
Additional cycles of immunization will be proposed to patients without tumor progression requiring another treatment. A second cycle of 3 injections at 6-week intervals will be started at week 17 with the same vaccine, followed by a third cycle of 12 injections at 3-month intervals starting at month 11. At any time, progression of the disease necessitating any treatment not allowed during the study, will result in study withdrawal.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Brussels, Belgium, B-1200
- Ludwig Institute for Cancer Research
-
Brussels, Belgium, B-1200
- Cliniques Universitaires Saint-Luc (UCL)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically proven cutaneous melanoma, or clear cell sarcoma, which is considered as a subtype of melanoma.
Melanoma must be at one of the following AJCC 2002 stages:
- Regional metastatic disease (any T; N2b, N2c or N3; M0).
- Distant metastatic disease (any T; any N; M1a, M1b or M1c), except brain or leptomeningeal localizations, and except elevated LDH.
- Patients must be HLA-A1.
- Melanoma must express the MAGE-3 gene, as determined by RT-PCR.
- Presence of at least one measurable or non-measurable tumor lesion, excluding leptomeningeal metastasis.
- Expected survival of at least 3 months.
- Karnofsky performance scale ≥70 or WHO performance status of 0 or 1.
Within the last 4 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which must be within the ranges specified:
Lab Parameter Range
- Hemoglobin ≥ 10 g/dl or ≥ 6,25 mmol/l
- Granulocytes ≥ 1,500/µl
- Lymphocytes ≥ 700/µl
- Platelets ≥ 100,000/µl
- Serum creatinine ≤ 2.0 mg/dl or ≤ 177 µmol/l
- Serum bilirubin ≤ 2.0 mg/dl or ≤ 34.2 µmol/l
- ASAT and ALAT ≤ 2 x the normal upper limits
- LDH ≤ the normal upper limit.
Viral tests:
- HIV (human immunodeficiency virus): negative antibodies.
- HBV (hepatitis B virus): negative antigens; antibodies may be positive.
- HCV (hepatitis C virus): negative antibodies.
- Age ≥ 18 years.
- Able and willing to give valid written informed consent.
Exclusion Criteria:
- Previous treatment with more than one regimen of systemic chemotherapy, combined or not with non-specific immunotherapy such as interferon alpha or interleukins. Chemoimmunotherapy or radiotherapy must be stopped within the preceding 4 weeks (6 weeks for nitrosoureas and mitomycin C).
- Previous treatment with a vaccine known or likely to contain the MAGE-3.A1 antigen, unless there is evidence that no CTL response against this antigen was induced by the vaccine.
- Clinically significant heart disease i.e. NYHA class 3 congestive heart failure; myocardial infarction within the past six months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
- Active immunodeficiency or autoimmune disease. Vitiligo is not an exclusion criterion.
- Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders, or other conditions requiring concurrent medications not allowed during this study.
- Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
- Lack of availability for immunological and clinical follow-up assessments.
- Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
- Pregnancy or breastfeeding.
- Women of childbearing potential: Refusal or inability to use effective means of contraception.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MAGE-3.A1 Peptide mixed with CpG 7909
Patients were vaccinated every two weeks on six occasions.
On each vaccination day, the MAGE-3.A1 peptide (300 mcg) mixed with CpG 7909 (5 mg) was administered twice intradermally (10% of the dose each) and twice subcutaneously (40% of the dose each) in the arms and thighs.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With a Detectable Cytolytic T Lymphocyte (CTL) Response Following Immunization With the MAGE-3.A1 Peptide Mixed With CpG 7909.
Time Frame: Up to 12 weeks
|
Blood samples were collected prior to treatment and in weeks 3, 7, and 13.
Specific CTL responses directed against the MAGE-3.A1 antigen were to be assessed by using restimulation in vitro, followed by staining with the A1/MAGE-3 tetramer and cloning of the tetramer-positive lymphocytes (MLPC/tetramer/cloning assay).
|
Up to 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To Determine the Safety of the Treatment by Measuring the Number of Patients With Dose Limiting Toxicities (DLT)
Time Frame: up to 12 weeks
|
All adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Scale, version 3.0. DLT was defined as:
|
up to 12 weeks
|
To Determine the Clinical Effectiveness of the Treatment by Measuring Tumor Response in Patients With Measurable Disease.
Time Frame: up to 12 weeks
|
Computed tomography (CT) scans were performed at screening, and at week 13.
Response was assessed using RECIST version 1.0 (Therasse et al, J Natl Cancer Inst 2000; 92:205-16).
Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions (no evaluable disease); partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria.
|
up to 12 weeks
|
Collaborators and Investigators
Investigators
- Study Chair: Nicolas van Baren, MD, Ludwig Institute for Cancer Research
- Study Director: Thierry BOON, PhD, Ludwig Institute for Cancer Research
Publications and helpful links
General Publications
- Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
- Marchand M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jager E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int J Cancer. 1999 Jan 18;80(2):219-30. doi: 10.1002/(sici)1097-0215(19990118)80:23.0.co;2-s.
- Germeau C, Ma W, Schiavetti F, Lurquin C, Henry E, Vigneron N, Brasseur F, Lethe B, De Plaen E, Velu T, Boon T, Coulie PG. High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens. J Exp Med. 2005 Jan 17;201(2):241-8. doi: 10.1084/jem.20041379.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LUD2002-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malignant Melanoma
-
National Cancer Institute (NCI)TerminatedRecurrent Melanoma | Stage IV Melanoma | Acral Lentiginous Malignant Melanoma | Lentigo Maligna Malignant Melanoma | Nodular Malignant Melanoma | Solar Radiation-related Skin Melanoma | Superficial Spreading Malignant MelanomaUnited States
-
Grupo Español Multidisciplinar de MelanomaGlaxoSmithKlineCompletedMalignant Melanoma Stage IV | Malignant Melanoma Stage IIIcSpain
-
Centre Hospitalier Universitaire de NiceUnknownMalignant Melanoma Stage III | Malignant Melanoma Stage IV
-
Hoffmann-La RocheCompletedMalignant Melanoma, NeoplasmsKorea, Republic of, Brazil, United States, Canada, Cyprus
-
Hoffmann-La RocheCompletedMalignant Melanoma, NeoplasmsSpain, New Zealand, Hungary, Serbia, Germany, Portugal, Netherlands, Greece, Australia
-
Dr. Ronnie ShapiraNot yet recruitingMetastatic Melanoma | Malignant Melanoma | Immunotherapy | Malignant Melanoma Stage IV | BRAF V600E
-
Hoffmann-La RocheCompletedMalignant Melanoma, CancerHungary
-
Hoffmann-La RocheCompletedMalignant Melanoma, NeoplasmsUnited States, South Africa, Croatia, Brazil, Egypt
-
Lynn E. Spitler, MDGenentech, Inc.; Celgene CorporationCompletedMetastatic Malignant MelanomaUnited States
-
National Cancer Institute (NCI)GlaxoSmithKline; Novartis PharmaceuticalsActive, not recruitingHematopoietic and Lymphoid Cell Neoplasm | Metastatic Melanoma | Stage IV Cutaneous Melanoma AJCC v6 and v7 | Locally Advanced Malignant Solid Neoplasm | Unresectable Malignant Solid Neoplasm | Locally Advanced Melanoma | Metastatic Malignant Solid Neoplasm | Stage IIIC Cutaneous Melanoma AJCC v7 | Unresectable...United States
Clinical Trials on MAGE-3.A1 peptide and CpG 7909
-
M.D. Anderson Cancer CenterCompleted
-
PfizerCompleted
-
University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Mucosal Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Ciliary Body and Choroid Melanoma, Small Size | Iris Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage... and other conditionsUnited States
-
Penn State UniversityWithdrawnNeuroblastoma | Osteogenic Sarcoma | Rhabdomyosarcoma
-
National Institute of Allergy and Infectious Diseases...Terminated
-
Centre Hospitalier Universitaire VaudoisLudwig Institute for Cancer ResearchCompleted
-
Ahmad TarhiniNational Cancer Institute (NCI)CompletedIntraocular Melanoma | Malignant Conjunctival Neoplasm | Melanoma (Skin)United States
-
University of AarhusAarhus University HospitalCompleted
-
Cliniques universitaires Saint-Luc- Université...TerminatedMetastatic MelanomaBelgium
-
National Institute of Allergy and Infectious Diseases...CompletedMalariaUnited States