IPI-Biotherapy for Patients With Metastatic Melanoma Previously Treated With Cytotoxic Drugs
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Progression Free survival (PFS)
研究概览
简要总结
The goal of the Phase I part of this clinical research study is to find the highest tolerable dose of the drug Yervoy (ipilimumab) that can be given with the drugs Intron-A (interferon alfa-2b) and Proleukin (aldesleukin, IL-2) to patients with metastatic melanoma. The safety of this combination will also be studied in Phase I. The goal of Phase II is to learn if this combination can help to control metastatic melanoma.
Ipilimumab, interferon alfa-2b, and aldesleukin are designed to block the activity of cells that decrease the immune system's ability to fight cancer.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 5 groups of 3-6 participants will be enrolled in the Phase I portion of the study, and up to 64 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of ipilimumab you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of ipilimumab. Each new group will receive a higher dose of ipilimumab than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ipilimumab is found.
If you are enrolled in the Phase II portion, you will receive ipilimumab at the highest dose that was tolerated in the Phase I portion.
All participants will receive the same dose level of interferon alfa-2b and aldesleukin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically documented diagnosis of advanced stage IV or unresectable stage III melanoma are eligible.
- •They should have recurrent melanoma with measurable or evaluable sites of disease, 1.0 cm or larger, in order to assess the response to treatment by the immune-related response criteria (irRC).
- •Phase I: Patients with prior therapy who do not have alternative treatment of higher priority will be eligible. Phase II: the patient may have been treated with cytotoxic drugs or targeted therapies but not with IL-2, interferon and anti-CTLA4 drugs for metastatic disease. Adjuvant ipilimumab will not be permitted. Only adjuvant interferon will be permitted. Prior radiation therapy for metastatic melanoma is permitted provided the patient has unirradiated metastatic sites for response evaluation and has fully recovered from its toxicity.
- •Patients between 18 years of age and 65 years of age with an ECOG performance status of 0, 1 or 2 will be eligible.
- •They should have normal blood counts with a white blood count (WBC) count of more than or equal to 3000/mm^3 an absolute neutrophil count of more than or equal to 1500/mm^3 and a platelet count of more than 100,000/mm^3 and have no impairment of renal function (serum creatinine less than 1.1 mg/dl for females and less than 1.4 mg/dl for males), hepatic function (serum bilirubin level of less than 1.2 mg/dl) and no evidence of significant cardiac or pulmonary dysfunction.
- •They should have no significant intercurrent illness such as an active infection associated with fever lasting more than 24 hours requiring antibiotics, uncontrolled psychiatric illness, hypercalcemia (calcium greater than 11 mg), or active gastrointestinal (GI) bleeding.
- •Females of child-bearing potential (non-childbearing is defined as greater than one year post-menopausal or surgically sterilized) must use acceptable contraceptive methods( abstinence, intrauterine device, oral contraceptive or double barrier devices) and must have a negative serum or urine pregnancy test within 14 days prior to beginning treatment on this trial. Sexually active men must also use acceptable contraceptive methods for the duration of time on study.
排除标准
- •Patients with bone metastases only.
- •Patients with brain metastases unless all of their metastatic brain lesions have been resected or treated with stereotactic radiotherapy with gamma rays and they are off corticosteroids. Patient should not have significant brain edema. Patients with spinal cord compression and leptomeningeal disease. No major surgery or radiation therapy within 21 days before starting treatment.
- •Patients with significant cardiac illness such as symptomatic coronary artery disease or previous history of myocardial infarction, impaired left ventricle function (Ejection Fraction less than 50%) on account of any organic disease such as hypertension or valvular heart disease or serious cardiac arrhythmia requiring therapy. Patients will be evaluated by the investigator or his designee.
- •Patients with significant impairment of pulmonary function on account of chronic bronchitis or chronic obstructive pulmonary disease (COPD) which has resulted in impairment of vital capacity of FEV1 to less than 65% of predicted normal values.
- •Patients with symptomatic effusions on account of pleural, pericardial or peritoneal metastases of melanoma.
- •Patients who are unable to return for follow-up visits as required by this study.
- •Patients with a history of second malignant tumor, other than the common skin cancers - basal and squamous carcinomas, within the past 3 years and uncertainty about the histological nature of the metastatic lesions. Cases with other types of malignancies should be reviewed and decided by the Principal Investigator (PI) of the study.
研究组 & 干预措施
Ipilimumab + Interferon + Interleukin-2
Ipilimumab starting dose 2 mg/kg intravenous (IV) day 1 only; IFN alfa-2b at 5 million U/m2 subcutaneously daily for 5 days starting day 1; IL-2 at 9 million IU/m^2 daily IV continuous infusion for 4 days on days 2-5.
干预措施: Ipilimumab (Drug)
Ipilimumab + Interferon + Interleukin-2
Ipilimumab starting dose 2 mg/kg intravenous (IV) day 1 only; IFN alfa-2b at 5 million U/m2 subcutaneously daily for 5 days starting day 1; IL-2 at 9 million IU/m^2 daily IV continuous infusion for 4 days on days 2-5.
干预措施: Interferon (Drug)
Ipilimumab + Interferon + Interleukin-2
Ipilimumab starting dose 2 mg/kg intravenous (IV) day 1 only; IFN alfa-2b at 5 million U/m2 subcutaneously daily for 5 days starting day 1; IL-2 at 9 million IU/m^2 daily IV continuous infusion for 4 days on days 2-5.
干预措施: Interleukin-2 (Aldesleukin) (Drug)
结局指标
主要结局
Progression Free survival (PFS)
时间窗: Assessed at 6-months then until disease progression or death.
Progression-free survival determined from the start of the study until disease progression or death, whichever is first and estimated using the method of Kaplan-Meier.
次要结局
未报告次要终点