Immunization With the MAGE-3.A1 Peptide Mixed With the Adjuvant CpG 7909 in Patients With Metastatic Melanoma

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00145145
• Collaborator: (none)
• Enrollment: 1
• Locations: 2
• Arm: 1
• Actual Duration (Months): 39.5
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purposes of this study are to determine whether immunization with the MAGE-3.A1 peptide mixed with CpG 7909 results in a detectable immune response; to determine the safety of this vaccine and to document the tumor response to the vaccine.

Condition or Disease	Intervention/Treatment	Phase
Malignant Melanoma	Biological: MAGE-3.A1 peptide and CpG 7909	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Immunization With the MAGE-3.A1 Peptide Mixed With the Immunological Adjuvant CpG 7909 in Patients With Metastatic Melanoma
• Actual Study Start Date: Jan 12, 2005
• Actual Primary Completion Date: Apr 7, 2005
• Actual Study Completion Date: Apr 28, 2008

Arms and Interventions

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.	Biological: MAGE-3.A1 peptide and CpG 7909

Outcome Measures

Primary Outcome Measures

1. Number of Patients With a Detectable Cytolytic T Lymphocyte (CTL) Response Following Immunization With the MAGE-3.A1 Peptide Mixed With CpG 7909. [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).

Secondary Outcome Measures

1. To Determine the Safety of the Treatment by Measuring the Number of Patients With Dose Limiting Toxicities (DLT) [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: 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 MAGE-3.A1 peptide mixed with CpG 7909.

2. To Determine the Clinical Effectiveness of the Treatment by Measuring Tumor Response in Patients With Measurable Disease. [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.

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-A1.

2. Melanoma must express the MAGE-3 gene, as determined by RT-PCR.

3. Presence of at least one measurable or non-measurable tumor lesion, excluding leptomeningeal metastasis.

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. 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.

3. 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).

4. Active immunodeficiency or autoimmune disease. Vitiligo is not an exclusion criterion.

5. 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.

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

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

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

9. Pregnancy or breastfeeding.

10. Women of childbearing potential: Refusal or inability to use effective means of contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cliniques Universitaires Saint-Luc (UCL)	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 van Baren, 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.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00145145
• Other Study ID Numbers: LUD2002-001
• First Posted: Sep 5, 2005
• Last Update Posted: Aug 4, 2021
• Last Verified: Aug 1, 2021

• 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: Melanoma; Vaccine; Peptide; MAGE; CpG
• Additional relevant MeSH terms: Melanoma

Study Results

Participant Flow

Arm/Group Title	MAGE-3.A1 Peptide Mixed With CpG 7909
Arm/Group Description	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.
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	MAGE-3.A1 Peptide Mixed With CpG 7909
Arm/Group Description	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.
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Region of Enrollment (participants) [Number]
Belgium	1 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With a Detectable Cytolytic T Lymphocyte (CTL) Response Following Immunization With the MAGE-3.A1 Peptide Mixed With CpG 7909.
Description	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).
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

The cytolytic T lymphocyte (CTL) response directed against the MAGE-3.A1 vaccine antigen was not analyzed due to the premature closing of this trial after only one patient was treated.

Arm/Group Title	MAGE-3.A1 Peptide Mixed With CpG 7909
Arm/Group Description	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.
Measure Participants	0

2. Secondary Outcome

Title	To Determine the Safety of the Treatment by Measuring the Number of Patients With Dose Limiting Toxicities (DLT)
Description	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: 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 MAGE-3.A1 peptide mixed with CpG 7909.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

The one patient who was entered into the study and received study treatment.

Arm/Group Title	MAGE-3.A1 Peptide Mixed With CpG 7909
Arm/Group Description	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.
Measure Participants	1
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	To Determine the Clinical Effectiveness of the Treatment by Measuring Tumor Response in Patients With Measurable Disease.
Description	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.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

The one patient who was entered into and treated in this study.

Arm/Group Title	MAGE-3.A1 Peptide Mixed With CpG 7909
Arm/Group Description	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.
Measure Participants	1
CR	0 0%
PR	0 0%
SD	0 0%
PD	1 100%

Adverse Events

Time Frame	up to 13 weeks
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 until end of study were documented. Toxicity was reported according to the Common Terminology Criteria for Adverse Events (CTCAE) Scale of the National Cancer Institute, version 3.0.
Arm/Group Title	MAGE-3.A1 Peptide Mixed With CpG 7909
Arm/Group Description	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.
All Cause Mortality
	MAGE-3.A1 Peptide Mixed With CpG 7909
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Serious Adverse Events
	MAGE-3.A1 Peptide Mixed With CpG 7909
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	MAGE-3.A1 Peptide Mixed With CpG 7909
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
General disorders
Pyrexia	1/1 (100%)
Influenza-like illness	1/1 (100%)
Night sweats	1/1 (100%)
Injection site pain	1/1 (100%)
Injection site erythema	1/1 (100%)
Injection site scab	1/1 (100%)
Fatigue	1/1 (100%)
Weakness	1/1 (100%)
Infections and infestations
Bronchitis	1/1 (100%)
Nervous system disorders
Headache	1/1 (100%)
Respiratory, thoracic and mediastinal disorders
Cough	1/1 (100%)
Hypoventilation	1/1 (100%)

Limitations/Caveats

Study terminated due to poor enrollment.

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.