A Phase I Study of Vorinostat in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 主要终点
- Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this Phase I study of vorinostat in combination with lenalidomide and dexamethasone in participants with relapsed or refractory multiple myeloma is to determine the maximum tolerated dose (MTD) as estimated by the incidence of dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D) as estimated by the incidence of drug-related adverse events (AEs).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Is a male or female at least 18 years old
- •Has relapsed or refractory MM and has had at least one prior therapy
- •Female participants of childbearing potential must have 2 negative serum pregnancy tests prior to receiving the first dose of study drugs
- •Female participants who can become pregnant must agree to use 2 separate forms of effective birth control at the same time, 4 weeks before, while taking, and for 4 weeks after stopping lenalidomide; post menopausal participants should be free from menses for >2 years, or are surgically sterilized
- •Male participant agrees to use an adequate method of contraception for the duration of the study, even if the participant has undergone a successful vasectomy
- •Male participants must agree to use a latex condom during sexual contact with a pregnant female or a female who can become pregnant; this is required for the duration of the study, and for 4 weeks after stopping therapy
- •Has at least 3 weeks washout prior to treatment
- •Is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis
排除标准
- •Has prior treatment with a histone deacetylase (HDAC) inhibitor
- •Has prior allogenetic bone marrow transplant
- •Has received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug
- •Uses illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse
- •Is pregnant or breast feeding or expecting to have a baby during the course of the study
- •Has human immunodeficiency virus (HIV) infection
- •Has Hepatitis B/C infection
- •Is currently receiving treatment for another type of cancer other than skin or cervical cancer that has not been in remission for 5 years or longer
研究组 & 干预措施
Level 1: Vorinostat 300 mg + lenalidomide 10 mg
Participants will receive vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Vorinostat (Drug)
Level 1: Vorinostat 300 mg + lenalidomide 10 mg
Participants will receive vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Level 1: Vorinostat 300 mg + lenalidomide 10 mg
Participants will receive vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Level 2: Vorinostat 400 mg + lenalidomide 10 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Vorinostat (Drug)
Level 2: Vorinostat 400 mg + lenalidomide 10 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Level 2: Vorinostat 400 mg + lenalidomide 10 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Level 3: Vorinostat 400 mg + lenalidomide 15 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Vorinostat (Drug)
Level 3: Vorinostat 400 mg + lenalidomide 15 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Level 3: Vorinostat 400 mg + lenalidomide 15 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Level 4: Vorinostat 400 mg + lenalidomide 20 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Vorinostat (Drug)
Level 4: Vorinostat 400 mg + lenalidomide 20 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Level 4: Vorinostat 400 mg + lenalidomide 20 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Level 5: Vorinostat 400 mg + lenalidomide 25 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Vorinostat (Drug)
Level 5: Vorinostat 400 mg + lenalidomide 25 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Level 5: Vorinostat 400 mg + lenalidomide 25 mg
Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
时间窗: Cycle 1 (Up to 28 days)
DLTs consisted of hematologic or non-hemtologic toxicities. Hematologic DLT was any grade (gr) 4 neutropenia lasting ≥7 days, gr 4 thrombocytopenia or gr 5 hematologic toxicity. Non-hematologic DLT was any gr 3, 4 or 5 non-hematologic toxicity with the exception of (1) gr 3 nausea, vomiting, diarrhea or dehydration not compliant with medical care, lasting \<48 hours (2) gr 3 acidosis/alkalosis returning to ≤ gr 2 by 48 hours of medical care (3) gr 3 liver function test elevation without symptoms, lasting ≤5 days (4) Gr 3 amylase elevation without symptoms (5) Gr 3 hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia or hyphosphatemia responding to medical care (6) Gr 3 hypercholeresterolemia or hypertriglyceridemia. A drug-related AE causing dose modification of study drug is also considered a DLT. Per protocol DLTs were analyzed in the first 28-day treatment cycle. The number of participants experiencing DLTs is reported here for all participants who got ≥1 dose of study drug.
次要结局
- Number of Participants Experiencing Drug-Related Adverse Events (AEs)(Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012))