A Phase I Trial of Ipilimumab (Anti CTLA- 4 Antibody) in Combination With Lenalidomide (IMiD) in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Ipilimumab in Combination With Lenalidomide
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of the combination of Yervoy® (ipilimumab) with Revlimid® (lenalidomide) that can be given to patients with advanced cancer. The safety of these drugs will also be studied.
Ipilimumab is designed to increase the immune system's ability to fight cancer.
Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. This may decrease the growth of cancer cells.
详细描述
Study Groups:
Dose escalation:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of the study drugs based on when you join the study.
Up to 5 dose levels of ipilimumab with lenalidomide will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ipilimumab with lenalidomide is found.
Dose expansion:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with advanced or metastatic cancers with no available standard therapy are eligible to enter the Phase 1 portion of this study.
- •Patients must be >/= 18 years.
- •Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. A confirmation (written or verbal) that there is no risk of surgical complications from a patient's surgeon has to be obtained prior to starting therapy in patients with a history of major surgery within past 6 weeks. Patients may have received palliative localized radiation immediately before or during treatment provided that radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be >/= 5 half-lives or >/= 3 weeks form the last dose (whichever comes first).
- •ECOG performance status </=
- •Patients must have adequate organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL platelets >/=50,000/mL; CrCl >/=60mL/min by Cockcroft -Gault calculation; total bilirubin </= 2x ULN (exceptions may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome); ALT(SGPT) </= 5X ULN; willingness to participate in the RevAssist® program. Females: two effective contraceptive methods should be used during therapy, during therapy interruptions, and for at least 4 weeks after completing therapy. Males: must always use a latex condom during any sexual contact with females of childbearing potential, even if they have undergone a successful vasectomy.
- •Patients must be able to understand and be willing to sign a written informed consent document.
排除标准
- •Uncontrolled intercurrent illness, including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
- •Pregnant or lactating women.
- •History of hypersensitivity to ipilimumab.
- •History of hypersensitivity to lenalidomide.
- •Patients unwilling or unable to sign informed consent document.
- •Patients on hemodialysis.
- •History of organ transplantation.
- •History of autoimmune disease, including inflammatory bowel disease.
- •History of severe motor or sensory neuropathy, or any other autoimmune disorder which is deemed to be significant.
- •Patients with a prior history of Grade 4 rash associated with thalidomide treatment.
- •History of Angioedema.
研究组 & 干预措施
Ipilimumab + Lenalidomide
Dose Escalation Group Ipilimumab Starting Dose: 1.5 mg by vein over 90 minutes on Day 1 of each 28 day cycle.
Dose Escalation Group Lenalidomide Starting Dose: 10 mg by mouth on Days 1-21 of each 28 day cycle.
Dose Expansion Group Starting Dose for Ipilimumab and Lenalidomide: Maximum tolerated dose (MTD) from Dose Escalation Groups.
干预措施: Ipilimumab (Drug)
Ipilimumab + Lenalidomide
Dose Escalation Group Ipilimumab Starting Dose: 1.5 mg by vein over 90 minutes on Day 1 of each 28 day cycle.
Dose Escalation Group Lenalidomide Starting Dose: 10 mg by mouth on Days 1-21 of each 28 day cycle.
Dose Expansion Group Starting Dose for Ipilimumab and Lenalidomide: Maximum tolerated dose (MTD) from Dose Escalation Groups.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Ipilimumab in Combination With Lenalidomide
时间窗: 28 days
Maximum tolerated dose (MTD) defined as highest dose studied in which the incidence of dose limiting toxicity (DLT) was less than 33%.
Dose-Limiting Toxicities (DLT) of Ipilimumab in Combination With Lenalidomide
时间窗: 28 days
Dose-limiting toxicity (DLT) defined as any clinically grade 3 or 4 non-hematologic toxicity as defined in NCI CTC v4.0, expected and believed to be related to study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens or alopecia), any grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI-CTC v4.0) or associated with bleeding and/or sepsis; any grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens, and any other grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in NCI-CTCAE v4.0 that is attributable to the therapy.
次要结局
- Tumor Response(Every 8 weeks)