A Phase 1 Study of ION251 Administered by Intravenous Infusion to Patients With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 6
- 主要终点
- Maximum-Tolerated Dose (MTD)
研究概览
简要总结
The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION251 in patients with relapsed/refractory multiple myeloma.
详细描述
This is a two-part, multi-center first in human study of ION251 in up to 80 participants. Part 1 will use a 3+3 dose-escalation scheme in sequential cohorts to determine the MTD and RP2D during repeated 28-day treatment cycles. MTD will be determined by the number of participants with AEs meeting the dose-limiting toxicity (DLT) criteria during Cycle 1. The MTD determined in Part 1 will be used with other variables to inform a RP2D for participants proceeding to Part 2 for further assessments in the safety, tolerability and anti-myeloma activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Aged ≥ 18 years at the time of informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Measurable multiple myeloma (MM)
- •In need of systemic treatment for MM and either is refractory to or has failed treatment with, is intolerant to or has refused, or is not otherwise a candidate in the opinion of the Investigator, for any of the currently available established therapies known to provide clinical benefit in relapsed/refractory MM. Refractory to treatment is defined as documented MM disease progression while on or within 60 days from the last dose (LD) of treatment
排除标准
- •Screen laboratory results as follows, or any other clinically significant abnormalities in screen laboratory values that would render a participant unsuitable for inclusion
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN)
- •Total bilirubin > 1.3 × ULN
- •Absolute neutrophil count ≤ 1.0 1000/cubic millimeter (k/mm^3)
- •Platelet count < 50 k/mm^3
- •Hemoglobin < 8.0 g/dL
- •Estimated glomerular filtration rate (eGFR) < 50 milliliters per minute (mL/min)/1.73 square meter (m^2)
- •Urine albumin creatinine ratio > 100 mg/g
- •History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone or extramedullary plasmacytoma as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm
- •Uncontrolled hypertension (systolic pressure ≥ 160 mm of mercury (mm Hg) and/or diastolic pressure ≥ 100 mm Hg)
- •Presence of a bleeding disorder or an underlying disease state associated with active bleeding.
研究组 & 干预措施
ION251
In Part 1, the dose escalation phase, increased amounts of ION251 will be administered at multiple time points by intravenous (IV) infusion during 28-day cycles. In Part 2, the determined RP2D of ION251 will be administered at multiple time points by IV infusion.
干预措施: ION251 (Drug)
结局指标
主要结局
Maximum-Tolerated Dose (MTD)
时间窗: Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 28 days)
MTD is defined as the maximum dose at which ≤ 1 of 3 evaluable participants experiences a dose-limiting toxicity (DLT) within Cycle 1 and there are 2 of 3 or 2 of 6 evaluable participants in the next higher-dose level experiencing a DLT within Cycle 1. If no dose in the dose-escalation has 2 of 3 or 2 of 6 evaluable participants experiencing a DLT, the highest dose level is considered the MTD
Recommended Phase 2 Dose (PR2D)
时间窗: Up to 28 days from the last dose of study drug
RP2D is chosen based on the dose response and exposure-response analyses of the pooled clinical PK, PD, safety results, and anti-myeloma activity from both Part 1 and Part 2
次要结局
- Safety and Tolerability as Measured by the Incidence of TEAEs(Up to 28 days from the last dose of study drug)
- Incidence of Abnormal Laboratory Values and Vital Signs(Up to 28 days from the last dose of study drug)
- Cmax: Maximum Observed Concentration ION251(From Baseline up to 28 days from the last dose of study drug)
- AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Hour zero to t of ION251(From Baseline up to 28 days from the last dose of study drug)
- t1/2: Distribution Half-life of ION251(From Baseline up to 28 days from the last dose of study drug)
- Trough Concentration of ION251(From Baseline up to 28 days from the last dose of study drug)
- Urine 0-24 Hour (hr) Excretion of ION251(Up to 12 months from the last dose of study drug)