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Phase I/II Study of Immunization With Multiple Peptides Mixed With the Immunological Montanide ISA 51 in HLA-A2 Patients With Metastatic Cutaneous Melanoma

Phase 1/Phase 2
18 Years
Not Enrolling
Malignant Melanoma

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Trial Information

Phase I/II Study of Immunization With Multiple Peptides Mixed With the Immunological Montanide ISA 51 in HLA-A2 Patients With Metastatic Cutaneous Melanoma

Patients will receive six sequential immunizations with 8 peptides presented by HLA-A2 and
mixed with Montanide, at 2-week intervals. The 8 peptides will 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).

300 µg of each peptide will be mixed with 0.5ml of Montanide.

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.

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,
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

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 cytolytic T lymphocyte (CTL) response against the vaccine, while the majority of
them does not so. 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.

Inclusion Criteria

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.

3. Patients must be HLA-A2.

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

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

6. Expected survival of at least 3 months.

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

8. 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 creatinin ≤ 2.0 mg/dl or ≤ 177 mmol/l

- Serum bilirubin ≤ 2.0 mg/dl or ≤ 34.2 mmol/l

- ASAT and ALAT ≤ 2 x the normal upper limits

- LDH ≤ the normal upper limit.

9. Viral tests:

- HIV (human immunodeficiency virus): negative antibodies.

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

- HCV (hepatitis C virus): negative antibodies.

10. Age ≥ 18 years

11. 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 is not an exclusion

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

- To describe the CTL response to individual peptides after immunization with a combination of 8 peptides and Montanide ISA-51.

Principal Investigator

Nicolas VanBaren, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Ludwig Institute for Cancer Research


Belgium: Ministry of Social Affairs, Public Health and the Environment

Study ID:




Start Date:

January 2005

Completion Date:

December 2009

Related Keywords:

  • Malignant Melanoma
  • Melanoma
  • Vaccine
  • Peptide
  • Montanide
  • Melanoma
  • Skin Neoplasms