Phase 1/1b Pharmacokinetics Study of Oral MLN9708 in Patients With Relapsed/Refractory Multiple Myeloma and Advanced Solid Tumors With Normal Renal Function or Severe Renal Impairment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 11
- 主要终点
- Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
研究概览
简要总结
The purpose of this study is to characterize the single-dose pharmacokinetic (PK) parameters of ixazomib (MLN9708) in cancer participants with either normal renal function or severe renal impairment (RI), including participants with end-stage renal disease (ESRD).
详细描述
The drug tested in this study was called ixazomib (MLN9708). Ixazomib was administered to participants with cancer and either normal renal function or severe renal impairment, including end-stage renal disease (ESRD) requiring hemodialysis. This study characterized the PK, safety and efficacy of ixazomib.
The study enrolled 41 participants (37 multiple myeloma and 4 advanced solid tumor). The study was conducted in 2 parts, Part A and Part B. Participants were enrolled to receive:
- Ixazomib 3.0 mg
In Part A, all participants were asked to take one 3 mg ixazomib capsule, orally on Day 1. Participants who tolerated ixazomib in Part A had the option of continuing the study by participating in Part B. In Part B, participants received ixazomib (4, 3, or 2.3 mg per protocol) on Days 1, 8, and 15 of each 28-day cycle until participants experienced disease progression or unacceptable toxicity.
This multicenter trial was conducted at 6 study sites in the United States and Canada. The overall time to participate in this study was 435 days. Participants made multiple scheduled visits to the clinic.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Male or female participants 18 years or older
- •Participants with multiple myeloma (MM) diagnosed according to standard criteria or participants with a diagnosis of an advanced malignant solid tumor for which standard, curative, or life prolonging treatment does not exist or is no longer effective. Participants with multiple myeloma must have had at least 1 prior therapy
- •A calculated creatinine clearance (CrCl) that meets entry criteria for enrollment (i.e., calculated CrCl either ≥ 90 mL/min for normal renal function or < 30 mL/min for severe renal impairment)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception through 90 days after the last dose of study drug or agree to practice true abstinence
- •Male participants who agree to practice effective barrier contraception through 90 after the last dose of study drug or agree to practice true abstinence
- •Voluntary written informed consent
- •Suitable venous access
排除标准
- •Female participants who are pregnant or lactating and breastfeeding
- •Failure to have recovered from clinically significant effects of prior chemotherapy (defined as toxicity greater than Grade 1 with the exception of alopecia)
- •Major surgery or radiotherapy within 14 days before study drug administration
- •Dexamethasone (or equivalent systemic steroid) higher than physiologic dosing within 7 days before study drug administration
- •Central nervous system involvement
- •Infection requiring IV antibiotic therapy or other serious infection within 14 days prior to first dose of study drug
- •Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, myeloproliferative syndrome, or primary amyloidosis (with the exception of patients in whom amyloidosis has been documented as a complication of MM, who will be evaluated on a case-by-case basis for trial participation)
- •Systemic treatment with strong and moderate inhibitors of Cytochrome P1A2 (CYP1A2), strong and moderate inhibitors of Cytochrome P3A (CYP3A), or clinically significant CYP3A inducers or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study drug
- •Evidence of uncontrolled cardiovascular conditions
- •Ongoing or active infection, or known human immunodeficiency virus (HIV) positive
- •Comorbid systemic illness or psychiatric illness that could interfere with study completion
- •Known allergy to study medications
- •Inability to swallow oral medication or condition that could interfere with oral absorption or tolerance of treatment
研究组 & 干预措施
Normal Renal Function: Ixazomib
In the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
干预措施: Ixazomib (Drug)
Severe Renal Impairment: Ixazomib
In the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
干预措施: Ixazomib (Drug)
End-stage Renal Disease: Ixazomib
In the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity.
干预措施: Ixazomib (Drug)
结局指标
主要结局
Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
时间窗: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
时间窗: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Unbound AUClast: Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
时间窗: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
次要结局
- Number of Participants With Adverse Events(From signing of first dose of study drug up to the 30 days after the last dose of study drug (approximately up to 885 days))
- Percentage of Participants With Overall Response (OR) in Relapsed/Refractory Multiple Myeloma (RRMM) Participants(Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days))
- Duration of Response (DOR) in RRMM Participants(Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days))