Immunization With 8 Peptides Mixed With CpG 7909 or Montanide ISA51 in Patients With Metastatic Cutaneous Melanoma

Sponsor
Ludwig Institute for Cancer Research (Other)
Overall Status
Terminated
CT.gov ID
NCT00145158
Collaborator
(none)
23
2
2
50.3
11.5
0.2

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
  • Biological: 8 HLA-A2-restricted peptides and Montanide ISA51
  • Biological: 8 HLA-A2-restricted peptides and CpG 7909
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

Study Type:
Interventional
Actual Enrollment :
23 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
The protocol planned the inclusion of 2 cohorts, each of them including 14 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).The protocol planned the inclusion of 2 cohorts, each of them including 14 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).
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/II Study of Immunization With Multiple Peptides Mixed With the Immunological Adjuvant CpG 7909 or Montanide ISA51 in HLA-A2 Patients With Metastatic Cutaneous Melanoma
Actual Study Start Date :
Jan 1, 2005
Actual Primary Completion Date :
Nov 30, 2007
Actual Study Completion Date :
Mar 12, 2009

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

  1. 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

  1. 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.

  2. 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.

  3. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion Criteria

  1. Histologically proven cutaneous melanoma, or clear cell sarcoma, which is considered as a subtype of melanoma.

  2. 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.

  1. Patients must be HLA-A2.

  2. A pre-immune tumor biopsy must be kept frozen for post-study PCR analysis.

  3. Presence of at least one measurable or non-measurable tumor lesion.

  4. Expected survival of at least 3 months.

  5. Karnofsky performance scale ≥70 or WHO performance status of 0 or 1.

  6. 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.

  1. Viral tests:
  • HIV (human immunodeficiency virus): negative antibodies.

  • HBV (hepatitis B virus): negative antigens; antibodies may be positive.

  • HCV (hepatitis C virus): negative antibodies.

  1. Age ≥ 18 years.

  2. Able and willing to give valid written informed consent.

Exclusion Criteria

  1. 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).

  2. 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.

  3. Active immunodeficiency or autoimmune disease. Vitiligo was not an exclusion criterion.

  4. 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.

  5. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.

  6. Lack of availability for immunological and clinical follow-up assessments.

  7. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.

  8. Pregnancy or breastfeeding.

  9. 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

Responsible Party:
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT00145158
Other Study ID Numbers:
  • LUD2003-007
First Posted:
Sep 5, 2005
Last Update Posted:
Apr 7, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Ludwig Institute for Cancer Research
Additional relevant MeSH terms:

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

1. Primary Outcome
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%
2. Secondary Outcome
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%
3. Secondary Outcome
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%
4. Secondary Outcome
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

[Not Specified]

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
Email mmacri@lcr.org
Responsible Party:
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT00145158
Other Study ID Numbers:
  • LUD2003-007
First Posted:
Sep 5, 2005
Last Update Posted:
Apr 7, 2022
Last Verified:
Apr 1, 2022