A Phase I Trial Testing Mart-1 Peptide Immunization in Malignant Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 1
研究概览
简要总结
RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage IV, or relapsed malignant melanoma.
详细描述
OBJECTIVES:
- Determine the safety of administering MART-1 peptide-pulsed dendritic cells to patients with stage IV or relapsed malignant melanoma.
- Determine the immunological and clinical responses in this patient population after this therapy.
OUTLINE: This is a dose-escalation study.
Patients undergo leukapheresis between days -14 to -8. Mononuclear cells are isolated, used to generate dendritic cells (DC), and then pulsed with MART-1 peptide. Patients are vaccinated with MART-1 peptide-pulsed DC either IV or intradermally on days 0, 14, and 28.
Cohorts of 3-6 patients receive escalating doses of MART-1 peptide-pulsed DC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •Adults over the age of 18 with malignant melanoma.
- •HLA-A2.1 positive and express MART-1, as assessed by either RT-PCR or by immunohistochemistry
- •Tumor stages T3N0M0 or greater are eligible for this trial according to the following:
- •I (<.75 to 1.5 mm or Clark level III-T1-2N0M0-)-not eligible
- •II (1.5 to 4 mm or level IV-T3N0M0-)-eligible
- •III (limited nodal metastasis involving one regional lymph node basin, or fewer than 5 in-transit metastasis -TxN1M0-)-eligible
- •IV (advanced regional metastasis -TxN2M0- or any distant metastasis -TxNxM1-)-eligible
- •Relapsed melanoma-eligible
- •Patients previously treated with any form of therapy for either metastatic, relapsed or primary melanoma are eligible for this trial, provided that previous treatment was completed >30 days prior to enrollment
- •Both male and females may be enrolled. Premenopausal females must have a negative pregnancy test prior to treatment
- •Karnofsky Performance Status greater than or equal to 70 percent
- •No previous evidence of class 3 or greater New York Heart Association cardiac insufficiency or coronary artery disease
- •No previous evidence of opportunistic infection
- •A minimum of 30 days must have elapsed since the completion of prior chemotherapy, immunotherapy or radiation therapy
- •Adequate baseline hematological function as assessed by the following laboratory values within 30 days prior to study entry (day -30 to 0):
- •Hemoglobin >9.0 g/dl
- •Platelets > 100000/mm3
- •WBC > 3000/mm3
- •Absolute Neutrophil Count > 1000/mm3
- •Positive skin test to common antigens (tetanus and candida)
- •Ability to give informed consent
排除标准
- •Lactating females and females of child-bearing potential must have negative serum beta-HCG pregnancy test
- •Acute infection: any acute viral, bacterial, or fungal infection which requires specific therapy. Acute therapy must have been completed within 14 days of prior to study treatment
- •HIV-infected patients
- •Acute medical problems such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk
- •Patients with any underlying conditions which would contraindicate therapy with study treatment (or allergies to reagents used in this study)
- •Patients with organ allografts
- •Uncontrolled CNS metastasis. Patients with CNS metastasis will be eligible if they have received CNS irradiation to control local tumor growth
研究组 & 干预措施
Group A
No. DC: 10^5 Route of Immunization: ID
干预措施: dendritic cell-MART-1 peptide vaccine (Biological)
Group A
No. DC: 10^5 Route of Immunization: ID
干预措施: leukapheresis (Procedure)
Group B
No. DC: 10^5 Route of Immunization: IV
干预措施: dendritic cell-MART-1 peptide vaccine (Biological)
Group B
No. DC: 10^5 Route of Immunization: IV
干预措施: leukapheresis (Procedure)
Group C
No. DC: 10^6 Route of Immunization: ID
干预措施: dendritic cell-MART-1 peptide vaccine (Biological)
Group C
No. DC: 10^6 Route of Immunization: ID
干预措施: leukapheresis (Procedure)
Group D
No. DC: 10^6 Route of Immunization: IV
干预措施: dendritic cell-MART-1 peptide vaccine (Biological)
Group D
No. DC: 10^6 Route of Immunization: IV
干预措施: leukapheresis (Procedure)
Group E
No. DC: 10^7 Route of Immunization: ID
干预措施: dendritic cell-MART-1 peptide vaccine (Biological)
Group E
No. DC: 10^7 Route of Immunization: ID
干预措施: leukapheresis (Procedure)
Group F
No. DC: 10^7 Route of Immunization: IV
干预措施: dendritic cell-MART-1 peptide vaccine (Biological)
Group F
No. DC: 10^7 Route of Immunization: IV
干预措施: leukapheresis (Procedure)