Immunization With 8 Peptides Mixed With CpG 7909 or Montanide ISA51 in Patients With Metastatic Cutaneous Melanoma
Study Details
Study Description
Brief Summary
The purposes of this study are to describe the immune response to individual peptides after immunization with a combination of 8 peptides and CpG 7909 or Montanide ISA51; to determine the safety of the vaccines and; to document the tumor response in patients receiving the vaccines.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Patients received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with either CpG 7909 or Montanide ISA51, at 2-week intervals. The 8 peptides were injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously).
300 µg of each peptide (except MAGE-10.A2 150 µg) was mixed with 4 mg CpG 7909 (Cohort 1) or 0.5ml of Montanide ISA51 (Cohort 2). In Cohort 2, the Tyrosinase.A2 was administered without Montanide ISA51.
Tumor staging was performed before inclusion and at week 13. Peripheral Blood Lymphocytes (PBL) collections were performed before starting the treatment, and at weeks 3, 7 and 13. They provided the T lymphocytes for the immunological analysis.
At week 13, the PCR results of the pre-immune tumor biopsy must be available. Additional cycles of immunization, ONLY with the peptides expressed by the tumor, mixed with Montanide ISA51, 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, 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 withdrawal.
The immune response may well be a limiting factor to the therapeutic efficacy of the vaccine. If this is the case, it then becomes crucial to understand why some patients develop a cytotoxic t-lymphocyte (CTL) response against the vaccine, while the majority of them do not. One possible explanation for the low frequency of clinical responses is that each injection of a single peptide has a low probability to provide the adequate stimulus to activate very rare CTL precursors. This probability should be increased if several peptides known to be undoubtedly associated with tumor regressions were used together to immunize patients.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Cohort 1: 8 HLA-A2-restricted peptides and CpG 7909 Patients were immunized with a combination of 8 peptides corresponding to defined tumor antigens (MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2, NY-ESO-1.A2, NA17.A2 and Tyrosinase.A2), mixed with CpG 7909. Patients received six sequential injections at 2-week intervals. |
Biological: 8 HLA-A2-restricted peptides and CpG 7909
|
Experimental: Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 Patients were immunized with a combination of 8 peptides corresponding to defined tumor antigens (MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2, NY-ESO-1.A2, and NA17.A2), mixed with Montanide ISA 51. Tyrosinase.A2 was administered without Montanide ISA51. Patients received six sequential injections at 2-week intervals. |
Biological: 8 HLA-A2-restricted peptides and Montanide ISA51
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Cytotoxic T-lymphocyte (CTL) Response to Individual Peptides After Immunization With a Combination of 8 Peptides and CpG 7909 or Montanide ISA51. [Week 13]
Peripheral blood lymphocytes (PBL) were collected prior to the first dose of vaccine and after the completion of the six vaccinations in Week 13. Specific CTL directed against the 8 vaccine antigens ( NA17.A2, MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 and Tyrosinase.A2) was assessed by using re-stimulation in vitro, followed by staining with the corresponding tetramer (MLPC/tetramer). A patient was considered to have a positive CTL response when the post-vaccine CTL response against at least one of the vaccine antigens was ten times higher than the corresponding pre-treatment value.
Secondary Outcome Measures
- Number of Patients With Dose Limiting Toxicities (DLT). [up to Week 13]
Toxicity was evaluated according to the National Cancer Institute (CTC Scale Version 3.0, published December 12, 2003). Dose limiting toxicity (DLT) is defined as: Any Grade 3 hematological or non-hematological toxicity other than skin or flu-like symptoms Any Grade 4 toxicity To be dose-limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent.
- Number of Patients With Tumor Responses After Immunization With a Combination of 8 Peptides and CpG 7909 or Montanide ISA51 as Measured by RECIST. [Week 13]
Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Tumor measurements were taken at screening and at the end of Cycle 1 in Week 13. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; 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.
- Number of Patients With Cytotoxic T-lymphocyte (CTL) Responses and Tumor Expression of the Corresponding Genes. [Week 13]
Gene expression was determined by RT-PCR on a pre-treatment tumor sample. The correlation of the induction of a CTL response against a defined antigen to the prior expression of the gene coding for this antigen by the tumor removed before vaccination was assessed.
Eligibility Criteria
Criteria
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-A2.
-
A pre-immune tumor biopsy must be kept frozen for post-study PCR analysis.
-
Presence of at least one measurable or non-measurable tumor lesion.
-
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).
-
Clinically significant heart disease (NYHA Class III or IV) 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 was 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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Clinique Universitaires St-Luc | Brussels | Belgium | B-1200 | |
2 | Ludwig Institute for Cancer Research | Brussels | Belgium | B-1200 |
Sponsors and Collaborators
- Ludwig Institute for Cancer Research
Investigators
- Study Chair: Nicolas VanBaren, MD, Ludwig Institute for Cancer Research
- Study Director: Thierry BOON, PhD, Ludwig Institute for Cancer Research
Study Documents (Full-Text)
None provided.More Information
Publications
- Germeau C, Ma W, Schiavetti F, Lurquin C, Henry E, Vigneron N, Brasseur F, Lethé 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.
- Marchand M, van Baren N, Weynants P, Brichard V, Dréno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Liénard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jäger 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.
- 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.
- LUD2003-007
Study Results
Participant Flow
Recruitment Details | The study was to recruit 28 patients; 14 in each group. The first subject was treated on January 18, 2005. The study was prematurely closed in November 2007 as 6 of the 8 peptides had expired. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 |
---|---|---|
Arm/Group Description | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with CpG 7909, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with Montanide ISA51, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). The Tyrosinase.A2 was administered without Montanide ISA51. |
Period Title: Overall Study | ||
STARTED | 16 | 7 |
COMPLETED | 14 | 4 |
NOT COMPLETED | 2 | 3 |
Baseline Characteristics
Arm/Group Title | Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 | Total |
---|---|---|---|
Arm/Group Description | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with CpG 7909, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with Montanide ISA51, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). The Tyrosinase.A2 was administered without Montanide ISA51. | Total of all reporting groups |
Overall Participants | 16 | 7 | 23 |
Age, Customized (Count of Participants) | |||
≥ to 18 years |
16
100%
|
7
100%
|
23
100%
|
Sex: Female, Male (Count of Participants) | |||
Female |
9
56.3%
|
5
71.4%
|
14
60.9%
|
Male |
7
43.8%
|
2
28.6%
|
9
39.1%
|
Region of Enrollment (participants) [Number] | |||
Belgium |
16
100%
|
7
100%
|
23
100%
|
Outcome Measures
Title | Number of Patients With Cytotoxic T-lymphocyte (CTL) Response to Individual Peptides After Immunization With a Combination of 8 Peptides and CpG 7909 or Montanide ISA51. |
---|---|
Description | Peripheral blood lymphocytes (PBL) were collected prior to the first dose of vaccine and after the completion of the six vaccinations in Week 13. Specific CTL directed against the 8 vaccine antigens ( NA17.A2, MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 and Tyrosinase.A2) was assessed by using re-stimulation in vitro, followed by staining with the corresponding tetramer (MLPC/tetramer). A patient was considered to have a positive CTL response when the post-vaccine CTL response against at least one of the vaccine antigens was ten times higher than the corresponding pre-treatment value. |
Time Frame | Week 13 |
Outcome Measure Data
Analysis Population Description |
---|
Patients who received at least six vaccinations and had samples taken at Week 13. |
Arm/Group Title | Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 |
---|---|---|
Arm/Group Description | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with CpG 7909, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with Montanide ISA51, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). The Tyrosinase.A2 was administered without Montanide ISA51. |
Measure Participants | 14 | 3 |
Patients with CTL Response |
6
37.5%
|
1
14.3%
|
Patients with no CTL Response |
8
50%
|
2
28.6%
|
Title | Number of Patients With Dose Limiting Toxicities (DLT). |
---|---|
Description | Toxicity was evaluated according to the National Cancer Institute (CTC Scale Version 3.0, published December 12, 2003). Dose limiting toxicity (DLT) is defined as: Any Grade 3 hematological or non-hematological toxicity other than skin or flu-like symptoms Any Grade 4 toxicity To be dose-limiting, an adverse event must be definitely, probably, or possibly related to the administration of the investigational agent. |
Time Frame | up to Week 13 |
Outcome Measure Data
Analysis Population Description |
---|
All patients who received at least one immunization. |
Arm/Group Title | Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 |
---|---|---|
Arm/Group Description | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with CpG 7909, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with Montanide ISA51, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). The Tyrosinase.A2 was administered without Montanide ISA51. |
Measure Participants | 16 | 7 |
Count of Participants [Participants] |
2
12.5%
|
0
0%
|
Title | Number of Patients With Tumor Responses After Immunization With a Combination of 8 Peptides and CpG 7909 or Montanide ISA51 as Measured by RECIST. |
---|---|
Description | Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Tumor measurements were taken at screening and at the end of Cycle 1 in Week 13. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; 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. |
Time Frame | Week 13 |
Outcome Measure Data
Analysis Population Description |
---|
Patients who received at least six immunizations and had tumor response measured at Week 13. |
Arm/Group Title | Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 |
---|---|---|
Arm/Group Description | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with CpG 7909, at 2-week intervals. The 8 peptides were injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with Montanide ISA51, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). The Tyrosinase.A2 was administered without Montanide ISA51. |
Measure Participants | 14 | 4 |
Complete Response (CR) |
0
0%
|
0
0%
|
Partial Response (PR) |
0
0%
|
0
0%
|
Stable Disease (SD) |
4
25%
|
0
0%
|
Progressive Disease (PD) |
10
62.5%
|
4
57.1%
|
Title | Number of Patients With Cytotoxic T-lymphocyte (CTL) Responses and Tumor Expression of the Corresponding Genes. |
---|---|
Description | Gene expression was determined by RT-PCR on a pre-treatment tumor sample. The correlation of the induction of a CTL response against a defined antigen to the prior expression of the gene coding for this antigen by the tumor removed before vaccination was assessed. |
Time Frame | Week 13 |
Outcome Measure Data
Analysis Population Description |
---|
Patients who had pretreatment tumor samples analyzed for gene expression, received at least six immunizations and had CTL responses at Week 13. |
Arm/Group Title | Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 |
---|---|---|
Arm/Group Description | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with CpG 7909, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with Montanide ISA51, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). The Tyrosinase.A2 was administered without Montanide ISA51. |
Measure Participants | 6 | 1 |
Count of Participants [Participants] |
3
18.8%
|
1
14.3%
|
Adverse Events
Time Frame | up to 45 months | |||
---|---|---|---|---|
Adverse Event Reporting Description | All adverse events (AEs) occurring during the study were to be documented in the source records and on the respective AE Case Report Form (CRF), regardless of the assumption of a causal relationship. All events, which occurred after signed informed consent, were to be documented. Toxicities were graded according to the scale of the National Cancer Institute, CTC Scale Version 3.0, published on December 12, 2003. | |||
Arm/Group Title | Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 | ||
Arm/Group Description | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with CpG 7909, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). | Patients with metastatic cutaneous melanoma, with at least one detectable metastasis (grades AJCC 2002 III N2b to N3, grades IV M1a, M1b, and M1c without elevation of the LDH rate and without central nervous system toxicity) received six sequential immunizations with 8 peptides presented by HLA-A2 and mixed with Montanide ISA51, at 2-week intervals. The 8 peptides were to be injected at 8 distinct injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously); NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously). The Tyrosinase.A2 was administered without Montanide ISA51. | ||
All Cause Mortality |
||||
Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/16 (0%) | 0/7 (0%) | ||
Serious Adverse Events |
||||
Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 7/16 (43.8%) | 3/7 (42.9%) | ||
Cardiac disorders | ||||
Bradycardia | 1/16 (6.3%) | 0/7 (0%) | ||
Injury, poisoning and procedural complications | ||||
Hip fracture | 0/16 (0%) | 1/7 (14.3%) | ||
Joint dislocation | 0/16 (0%) | 1/7 (14.3%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Metastatic malignant melanoma | 3/16 (18.8%) | 0/7 (0%) | ||
Tumor haemorrhage | 1/16 (6.3%) | 0/7 (0%) | ||
Infected neoplasm | 0/16 (0%) | 1/7 (14.3%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Pleural effusion | 1/16 (6.3%) | 0/7 (0%) | ||
Skin and subcutaneous tissue disorders | ||||
Angioedema | 1/16 (6.3%) | 0/7 (0%) | ||
Vascular disorders | ||||
Deep vein thrombosis | 1/16 (6.3%) | 0/7 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Cohort 1: 8 HLA-A2-restricted Peptides and CpG 7909 | Cohort 2: 8 HLA-A2-Restricted Peptides and Montanide ISA51 | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 16/16 (100%) | 7/7 (100%) | ||
Cardiac disorders | ||||
Supraventricular extrasystoles | 1/16 (6.3%) | 1/7 (14.3%) | ||
Tachycardia | 1/16 (6.3%) | 0/7 (0%) | ||
Gastrointestinal disorders | ||||
Diarrhoea | 3/16 (18.8%) | 1/7 (14.3%) | ||
Abdominal pain | 2/16 (12.5%) | 0/7 (0%) | ||
Nausea | 2/16 (12.5%) | 0/7 (0%) | ||
Vomiting | 2/16 (12.5%) | 0/7 (0%) | ||
Abdominal pain lower | 1/16 (6.3%) | 0/7 (0%) | ||
Abdominal pain upper | 1/16 (6.3%) | 0/7 (0%) | ||
Constipation | 1/16 (6.3%) | 0/7 (0%) | ||
Dry mouth | 1/16 (6.3%) | 0/7 (0%) | ||
Dysphagia | 1/16 (6.3%) | 0/7 (0%) | ||
Lip oedema | 1/16 (6.3%) | 0/7 (0%) | ||
General disorders | ||||
Injection site erythema | 16/16 (100%) | 6/7 (85.7%) | ||
Injection site pain | 14/16 (87.5%) | 2/7 (28.6%) | ||
Injection site induration | 11/16 (68.8%) | 2/7 (28.6%) | ||
Fatigue | 8/16 (50%) | 3/7 (42.9%) | ||
Pyrexia | 9/16 (56.3%) | 1/7 (14.3%) | ||
Injection site warmth | 8/16 (50%) | 1/7 (14.3%) | ||
Influenza like illness | 6/16 (37.5%) | 0/7 (0%) | ||
Injection site pruritus | 4/16 (25%) | 2/7 (28.6%) | ||
Asthenia | 5/16 (31.3%) | 0/7 (0%) | ||
Malaise | 4/16 (25%) | 1/7 (14.3%) | ||
Injection site oedema | 3/16 (18.8%) | 1/7 (14.3%) | ||
Injection site swelling | 2/16 (12.5%) | 2/7 (28.6%) | ||
Injection site reaction | 1/16 (6.3%) | 2/7 (28.6%) | ||
Injection site ulcer | 3/16 (18.8%) | 0/7 (0%) | ||
Axillary pain | 2/16 (12.5%) | 0/7 (0%) | ||
Chills | 2/16 (12.5%) | 0/7 (0%) | ||
Nodule | 2/16 (12.5%) | 0/7 (0%) | ||
Pain | 2/16 (12.5%) | 0/7 (0%) | ||
Peripheral swelling | 2/16 (12.5%) | 0/7 (0%) | ||
Chest pain | 1/16 (6.3%) | 0/7 (0%) | ||
Illness | 1/16 (6.3%) | 0/7 (0%) | ||
Injection site erosion | 1/16 (6.3%) | 0/7 (0%) | ||
Injection site inflammation | 0/16 (0%) | 1/7 (14.3%) | ||
Injection site joint pain | 1/16 (6.3%) | 0/7 (0%) | ||
Injection site scab | 1/16 (6.3%) | 0/7 (0%) | ||
Injection site vesicles | 1/16 (6.3%) | 0/7 (0%) | ||
Mass | 1/16 (6.3%) | 0/7 (0%) | ||
Oedema peripheral | 0/16 (0%) | 1/7 (14.3%) | ||
Vessel puncture site bruise | 1/16 (6.3%) | 0/7 (0%) | ||
Immune system disorders | ||||
Hypersensitivity | 1/16 (6.3%) | 0/7 (0%) | ||
Infections and infestations | ||||
Urinary tract infection | 1/16 (6.3%) | 1/7 (14.3%) | ||
Cystitis | 1/16 (6.3%) | 0/7 (0%) | ||
Folliculitis | 0/16 (0%) | 1/7 (14.3%) | ||
Gastroenteritis | 0/16 (0%) | 1/7 (14.3%) | ||
Influenza | 1/16 (6.3%) | 0/7 (0%) | ||
Nasopharyngitis | 0/16 (0%) | 1/7 (14.3%) | ||
Scrotal infection | 1/16 (6.3%) | 0/7 (0%) | ||
Injury, poisoning and procedural complications | ||||
Vaccination complication | 2/16 (12.5%) | 0/7 (0%) | ||
Investigations | ||||
General physical condition abnormal | 6/16 (37.5%) | 0/7 (0%) | ||
Weight decreased | 4/16 (25%) | 2/7 (28.6%) | ||
Respiratory rate increased | 3/16 (18.8%) | 1/7 (14.3%) | ||
Antinuclear antibody positive | 3/16 (18.8%) | 0/7 (0%) | ||
Blood lactate dehydrogenase increased | 2/16 (12.5%) | 0/7 (0%) | ||
Karnofsky scale worsened | 2/16 (12.5%) | 0/7 (0%) | ||
Blood bilirubin increased | 1/16 (6.3%) | 0/7 (0%) | ||
C-reactive protein increased | 1/16 (6.3%) | 0/7 (0%) | ||
Glucose urine present | 1/16 (6.3%) | 0/7 (0%) | ||
Heart rate increased | 1/16 (6.3%) | 0/7 (0%) | ||
Inflammatory marker increased | 1/16 (6.3%) | 0/7 (0%) | ||
Karnofsky scale | 1/16 (6.3%) | 0/7 (0%) | ||
Weight increased | 0/16 (0%) | 1/7 (14.3%) | ||
Metabolism and nutrition disorders | ||||
Decreased appetite | 7/16 (43.8%) | 1/7 (14.3%) | ||
Appetite disorder | 1/16 (6.3%) | 0/7 (0%) | ||
Hypocalcaemia | 1/16 (6.3%) | 0/7 (0%) | ||
Hypokalaemia | 0/16 (0%) | 1/7 (14.3%) | ||
Musculoskeletal and connective tissue disorders | ||||
Myalgia | 4/16 (25%) | 0/7 (0%) | ||
Pain in extremity | 2/16 (12.5%) | 2/7 (28.6%) | ||
Arthralgia | 3/16 (18.8%) | 0/7 (0%) | ||
Back pain | 2/16 (12.5%) | 0/7 (0%) | ||
Flank pain | 1/16 (6.3%) | 0/7 (0%) | ||
Groin pain | 1/16 (6.3%) | 0/7 (0%) | ||
Muscle spasms | 0/16 (0%) | 1/7 (14.3%) | ||
Muscular weakness | 0/16 (0%) | 1/7 (14.3%) | ||
Musculoskeletal stiffness | 1/16 (6.3%) | 0/7 (0%) | ||
Neck pain | 1/16 (6.3%) | 0/7 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Tumor pain | 4/16 (25%) | 0/7 (0%) | ||
Tumor ulceration | 1/16 (6.3%) | 1/7 (14.3%) | ||
Metastatic malignant melanoma | 1/16 (6.3%) | 0/7 (0%) | ||
Nervous system disorders | ||||
Headache | 4/16 (25%) | 1/7 (14.3%) | ||
Hypoaesthesia | 2/16 (12.5%) | 0/7 (0%) | ||
Dizziness | 1/16 (6.3%) | 0/7 (0%) | ||
Dysstasia | 0/16 (0%) | 1/7 (14.3%) | ||
Hyperaesthesia | 1/16 (6.3%) | 0/7 (0%) | ||
Paraesthesia | 1/16 (6.3%) | 0/7 (0%) | ||
Sciatica | 1/16 (6.3%) | 0/7 (0%) | ||
Psychiatric disorders | ||||
Insomnia | 4/16 (25%) | 1/7 (14.3%) | ||
Depression | 3/16 (18.8%) | 1/7 (14.3%) | ||
Anxiety | 2/16 (12.5%) | 0/7 (0%) | ||
Depressed mood | 0/16 (0%) | 2/7 (28.6%) | ||
Nervousness | 0/16 (0%) | 1/7 (14.3%) | ||
Renal and urinary disorders | ||||
Haematuria | 1/16 (6.3%) | 0/7 (0%) | ||
Heamorrhage urinary tract | 1/16 (6.3%) | 0/7 (0%) | ||
Reproductive system and breast disorders | ||||
Breast pain | 1/16 (6.3%) | 0/7 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Dyspnoea | 2/16 (12.5%) | 0/7 (0%) | ||
Cough | 1/16 (6.3%) | 0/7 (0%) | ||
Epistaxis | 1/16 (6.3%) | 0/7 (0%) | ||
Pulmonary pain | 0/16 (0%) | 1/7 (14.3%) | ||
Rales | 1/16 (6.3%) | 0/7 (0%) | ||
Respiration abnormal | 1/16 (6.3%) | 0/7 (0%) | ||
Rhinorrhoea | 0/16 (0%) | 1/7 (14.3%) | ||
Skin and subcutaneous tissue disorders | ||||
Pruritus | 2/16 (12.5%) | 2/7 (28.6%) | ||
Acne | 1/16 (6.3%) | 0/7 (0%) | ||
Ecchymosis | 0/16 (0%) | 1/7 (14.3%) | ||
Erythema | 0/16 (0%) | 1/7 (14.3%) | ||
Hyperkeratosis | 0/16 (0%) | 1/7 (14.3%) | ||
Vascular disorders | ||||
Hypertension | 3/16 (18.8%) | 1/7 (14.3%) | ||
Hypotension | 2/16 (12.5%) | 0/7 (0%) | ||
Haemorrhage | 1/16 (6.3%) | 0/7 (0%) | ||
Hot flush | 0/16 (0%) | 1/7 (14.3%) | ||
Orthostatic hypotension | 0/16 (0%) | 1/7 (14.3%) | ||
Peripheral venous disease | 1/16 (6.3%) | 0/7 (0%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Mary Macri, Senior Director, Clinical Trials Management |
---|---|
Organization | Ludwig Institute for Cancer Research |
Phone | 12124501546 |
mmacri@lcr.org |
- LUD2003-007