Immunization of Disease-Free Melanoma Patients With Different HLA-A2 Peptides
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Primary: Determination of the cytolytic T lymphocyte response in the different arms.; Toxicity of the combination peptide and immunological adjuvants
研究概览
简要总结
Open-label single center study. Patients will be divided in four groups of 7. Group 1: 8 melanoma-specific peptides in saline; Group 2: same mix of peptides + Montanide ISA51; Group 3: same mix of peptides + IMP321 500 µg; Group 4: same mix of peptides + IMP321 500 µg + Montanide ISA51. These vaccines will be administered every 3 weeks on 5 occasions by intradermal and superficial subcutaneous injections.
详细描述
Open-label single center study. Patients will be divided in four groups of 7. The patients will be entered sequentially at the time they present in clinic, and randomized in one of the four groups.
The first group of patients will receive a dose of 300 µg of each of the MAGE-1.A2, MAGE-3.A2, MAGE-4.A2, MAGE-10.A2, MAGE-C2.A2, NA17.A2, Tyrosinase.A2 and NY-ESO-1.A2 peptides without adjuvant. The peptides will be mixed together and administered by intradermal and superficial subcutaneous injections at two sites every three weeks on 5 occasions (3 months).
The second group of patients will receive on 5 occasions a vaccine containing the same 8 peptides mixed together but emulsified in 1 ml of Montanide ISA51. This vaccine will be also administered by intradermal and subcutaneous injections every three weeks.
The third cohort of patients will receive at 3 weeks-interval on 5 occasions the mix of 8 peptides and 500 µg of IMP321. These two injections will be done at the same site, first adjuvant IMP321 then the peptides.
The last seven patients will receive as vaccine the same mix of peptides emulsified with Montanide ISA 51 VG and IMP321 injected with the same procedure as cohort 3. These vaccines will be administrated every 3 weeks on 5 occasions by intradermal and superficial subcutaneous injections.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven cutaneous melanoma.
- •Patient's melanoma must be in one of the following AJCC stages :
- •only primary tumor : T3b-T4, N0, M
- •regional lymph node metastasis and/or in-transit metastasis, no distant metastasis (any T, N1-N3, M0) that has been removed.
- •Any distant metastasis that has been removed (M1) HLA-A2 positive. Patients with previous regional metastatic disease must have one of their resected lesions analyzed by RT-PCR to determine expression of genes MAGE-1, MAGE-3, MAGE-4, MAGE-10, MAGE-C2, NA17, Tyrosinase or NY-ESO-
- •However, expression of these genes by the tumor is not required to enter the study.
- •Absence of detectable melanoma lesions. WHO/ECOG performance status of 1 or less (Karnofsky scale ≥ 70%).
- •The following laboratory results:
- •Hemoglobin ≥ 10 g/dl; Neutrophils ≥ 1,500/µl; Lymphocytes ≥ 700/µl; Platelets ≥ 100,000/µl; Serum creatinin ≤ 2.0 mg/dl; Serum bilirubin ≤ 2.0 mg/dl; LDH within normal institutional limits.
- •Age > 18 years. Able to give written informed consent.
排除标准
- •Clinically significant heart disease (NYHA Class III or IV). Other serious illnesses, e.g. serious infections requiring antibiotics, bleeding disorders, a second active malignancy, except basal cell carcinoma or in situ carcinoma of the uterine cervix.
- •Active immunodeficiency disease or autoimmune disease. Positive serology for HIV (human immunodeficiency virus) or HCV (hepatitis C virus). Serum hepatitis B antigen (HBsAg) must be negative.
- •More than one line of previous chemotherapy, or immunotherapy for the melanoma. Previous vaccination with one of the antigen present in the vaccine. Treatment with steroids or major immunosuppressive drugs within 4 weeks before study entry. Topical or inhalational steroids are permitted.
- •Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
- •Pregnancy or lactation. Women of childbearing potential not using a medically acceptable means of contraception.
- •Psychiatric or addictive disorders that may compromise the ability to give informed consent.
- •Lack of availability of the patient for immunological and clinical follow-up assessment.
研究组 & 干预措施
Group B
The eight HLA-A2 peptides + immunological adjuvant Montanide ISA51
干预措施: Montanide ISA51 (Biological)
Group A
The eight HLA-A2 peptides
干预措施: Immunological peptides and immunological adjuvants (Biological)
Group A
The eight HLA-A2 peptides
干预措施: HLA-A2 peptides (Biological)
Group B
The eight HLA-A2 peptides + immunological adjuvant Montanide ISA51
干预措施: Immunological peptides and immunological adjuvants (Biological)
Group B
The eight HLA-A2 peptides + immunological adjuvant Montanide ISA51
干预措施: HLA-A2 peptides (Biological)
Group C
the eight peptides HLA-A2 + IMP321
干预措施: Immunological peptides and immunological adjuvants (Biological)
Group C
the eight peptides HLA-A2 + IMP321
干预措施: HLA-A2 peptides (Biological)
Group D
The eight HLA-A2 peptides + the 2 immunological adjuvants (Montanides ISA 51 and IMP321)
干预措施: HLA-A2 peptides (Biological)
Group D
The eight HLA-A2 peptides + the 2 immunological adjuvants (Montanides ISA 51 and IMP321)
干预措施: Immunological peptides and immunological adjuvants (Biological)
Group C
the eight peptides HLA-A2 + IMP321
干预措施: IMP321 (Biological)
Group D
The eight HLA-A2 peptides + the 2 immunological adjuvants (Montanides ISA 51 and IMP321)
干预措施: Montanide ISA51 (Biological)
Group D
The eight HLA-A2 peptides + the 2 immunological adjuvants (Montanides ISA 51 and IMP321)
干预措施: IMP321 (Biological)
结局指标
主要结局
Primary: Determination of the cytolytic T lymphocyte response in the different arms.; Toxicity of the combination peptide and immunological adjuvants
次要结局
- Secondary: Disease-free survival.