Immunotherapy of Stage III/IV Melanoma Patients

Vaud University Hospital Center

Status and phase: Completed; Phase 1

Conditions: Melanoma

Treatments: Biological: Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG+ IL-2; Biological: Melan-A ELA + Montanide; Biological: Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG; Biological: Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide; Biological: Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG

Study type: Interventional

Funder types: Other

Identifiers

NCT00112242

LUD 2001-003

Details and patient eligibility

About

The purpose of this study is to determine whether vaccination with melanoma antigen peptides [Melan-A/Mart-1 (both EAA and ELA), NY-ESO-1b analog, Long NY-ESO-1 LP and MAGE-A10] and Montanide, CpG adjuvants and low dose rIL-2 can induce an immune response in melanoma patients and to assess the safety of this vaccination.

Full description

Current peptide vaccines suffer from low efficiency, since they induce only weak immune activation. We have recently confirmed that in humans the immune response was readily detectable in local lymph nodes while no or only weak activation could be identified in circulating lymphocytes. Increased doses of antigen and adjuvant allow a better extension from local to systemic immune responses.

• Group 1 : vaccination with Melan-A analog (ELA) peptide + Montanide
• Group 2 : vaccination with Melan-A analog (ELA), NY-ESO-1b analog and MAGE-A10 peptides + Montanide
• Group 3: vaccination with Melan-A analog (both EAA and ELA), Mage-A10, NY-ESO-1 peptides+ Montanide + CpG adjuvant
• Group 4: vaccination with Melan-A (ELA), Mage-A10,long NY-ESO-1LP peptides + Montanide + CpG
• Group 5: vaccination with Melan-A (both EAA and ELA), Mage-A10, long NY-ESO-1 LP peptides + Montanide + CpG + low dose rIL-2

Enrollment: 39 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically confirmed stage III or stage IV melanoma with at least one metastatic lymph node and/or at least one in-transit metastasis. According to the AJCC rules, this includes all patients with stage IV and stage III. Patients with or without measurable disease may be included.

2. Tumor expression of Melan-A by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis for patients of group I.

   Tumor expression of Melan-A and at least one of the tumor antigens MAGE-A10, NY-ESO-1, or LAGE-1 by rt-PCR analysis for patients of group II and III and for HLA-A2+ patients of groups IV and V. HLA-A2 negative patients of groups IV and V must only have NY-ESO-1 positive tumors to be eligible, while expression of Melan-A and MAGE-A10 is unimportant.

   If no frozen tissue is available, immunohistochemistry may be performed to detect tumor expression of Melan-A and NY-ESO-1.

3. HLA-A2 positive (serological or molecular typing of Peripheral Blood Lymphocytes (PBL) for patients of groups 1 to 3. Patients of groups 4 and 5 may either be HLA-A2+ or HLA-A2-.

4. Expected survival of at least five months.

5. Full recovery from surgery.

6. Karnofsky scale performance status of 70% or more.

7. The following laboratory results:

   Neutrophil count sup or equal 2.0 x 10^9/L Lymphocyte count sup or equal 0.5 x 10^9/L Platelet count sup or equal 100 x 10^9/L Creatinine ≤ 2 mg/dL (180 micromol/L) Bilirubin ≤ 2mg/dL (34 micromol/L) Granulocyte count > 2.5x10^9/L AST < 2x upper limit of normal aPTT: within the normal ranges of the laboratory ± 25 %

8. Age > 18 years.

9. Able to give written informed consent.

Exclusion criteria

1. Clinically significant heart disease (NYHA Class III or IV).
2. Other serious illnesses, e.g., serious infections requiring antibiotics, uncontrolled peptic ulcer, or central nervous system disorders with major dysfunction.
3. History of immunodeficiency disease or autoimmune disease.
4. Known HIV positivity.
5. Known seropositivity for hepatitis B surface antigen.
6. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
7. Concomitant treatment with steroids, antihistamine drugs. Topical or inhalational steroids are permitted.
8. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
9. Pregnancy or lactation.
10. Women of childbearing potential not using a medically acceptable means of contraception.
11. Psychiatric or addictive disorders that may compromise the ability to give informed consent.
12. Lack of availability of the patient for immunological and clinical follow-up assessment.
13. Coagulation or bleeding disorders.
14. Metastatic disease to the central nervous system, unless treated and stable.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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39 participants in 5 patient groups

1. Melan-A ELA

Experimental group

Description:

500 mcg Melan-A ELA analog peptide + 1 ml Montanide ISA-51

Treatment:

Biological: Melan-A ELA + Montanide

2. Melan-A ELA + NY-ESO-1b + MAGE-A10

Experimental group

Description:

500 mcg Melan-A ELA analog peptide + 500 mcg NY-ESO-1b(A) analog peptide + 500 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51

Treatment:

Biological: Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide

3. Melan-A ELA + NY-ESO-1b + MAGE-A10 + CpG

Experimental group

Description:

500 mcg Melan-A ELA analog peptide + 500 mcg NY-ESO-1b(A) analog peptide + 500 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 + 2.5 mg CpG-7909/PF-3512676

Treatment:

Biological: Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG

4. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG

Experimental group

Description:

* If patient is HLA-A2 positive: 100 mcg Melan-A EAA native peptide (during first cycle) or 100 mcg ELA analog peptide (during other cycles) + 500 mcg NY-ESO-1lp long peptide + 100 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 * If patient is HLA-A2 negative: 500 mcg NY-ESO-1lp long peptide+ 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676

Treatment:

Biological: Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG

5. Melan-A EAA/ELA + NY-ESO-1lp + MAGE-A10+ CpG+ IL-2

Experimental group

Description:

* If patient is HLA-A2 positive: 100 mcg Melan-A EAA native peptide (during first cycle) or 100 mcg ELA analog peptide (during other cycles) + 500 mcg NY-ESO-1lp long peptide + 100 mcg MAGE-A10 peptide + 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 + low dose IL-2 * If patient is HLA-A2 negative: 500 mcg NY-ESO-1lp long peptide+ 1 ml Montanide ISA-51 (no Montanide during cycle 3) + 2.5 mg CpG-7909/PF-3512676 + low dose IL-2

Treatment:

Biological: Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG+ IL-2