A Phase 1, Open-label Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 12
- 主要终点
- Occurrence of SAE (serious adverse events)
研究概览
简要总结
The purpose of this study is to assess the safety, pharmacokinetics and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI2228 in adult subjects with multiple myeloma who are either transplant ineligible or post autologous stem cell transplant and are relapsed/refractory.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open-label
入排标准
- 年龄范围
- 18 Years 至 101 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be ≥ 18 years of age at the time of screening.
- •Subjects must have a confirmed diagnosis of relapsed/refractory MM as per IMWG criteria (Rajkumar et al, 2014) and have exhausted standard of care regimens with proven clinical benefit, which include agents from the following anti myeloma therapies: PIs, IMIDs, and mAbs and have measurable disease with at least one of the following criteria:
- •Serum M-protein ≥ 0.5 g/dL
- •Urine M-protein ≥ 200 mg/24 hours
- •Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal.
- •Subjects must either be ineligible for or post-autologous stem cell transplant.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Adequate organ and marrow functions as determined per protocol-defined criteria.
- •Exclusion Criteria
- •Any of the following would exclude the subject from participation in the study:
- •Target Disease:
- •Subjects who have previously received an autologous stem cell transplant if less than 90 days have elapsed from the time of transplant or the subject has not recovered from transplant associated toxicities prior to the first scheduled dose of MEDI2228
- •Subjects who have previously received an allogeneic stem cell transplant
- •Central nervous system (CNS) involvement(including meningeal involvement) by MRI or cerebrospinal fluid exam
- •Known history of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome, plasma cell leukemia, Waldenstrom's macroglobulinemia, or amyloidosis
- •Medical History and Concurrent Diseases:
- •Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
排除标准
- 未提供
结局指标
主要结局
Occurrence of SAE (serious adverse events)
时间窗: From time of informed consent through 90 days post end of treatment
To assess the occurrence of serious adverse events (SAEs)
Number of patients with changes in vital signs from baseline
时间窗: From time of informed consent and up to 21 days post end of treatment
To assess body temperature, blood pressure and heart rate
Number of patients with changes in elctrocardiogram (ECG) results from baseline
时间窗: From time of informed consent and up to 21 days post end of treatment
To assess using 12 lead ECG recordings
Occurrence of DLTs (dose limiting toxicities)
时间窗: From time of informed consent through 90 days post end of treatment
To assess by the occurrence of hematologic and non-hematologic toxicities, AEs, and abnormal laboratory results
Occurrence of adverse events (AEs)
时间窗: From time of informed consent through 90 days post end of treatment
To assess by the occurrence of adverse events (AEs)
Number of patients with changes in laboratory parameters from baseline
时间窗: From time of informed consent and up to 21 days post end of treatment
To assess serum chemistry, hematology, coagulation and urninalysis
次要结局
- Duration of response (DoR)(From time of informed consent and up to three years after final patient is enrolled)
- MEDI2228 terminal half-life for PK(From time of informed consent through 60 days post end of treatment)
- Number of subjects who develop anti-drug antibodies (ADAs)(From time of informed consents through 60 days post end of treatment)
- Clinical benefit rate(From time of informed consent up to three years after final patient is enrolled)
- Progression free survival (PFS)(From time of informed consent and up to three years after final patient is enrolled)
- MEDI2228 maximum observed concentration for PK(From time of informed consent through 60 days post end of treatment)
- MEDI2228 area under the concentration-time curve for PK(From time of informed consent through 60 days post end of treatment)
- MEDI2228 clearance for PK(From time of informed consent through 60 days post end of treatment)
- Objective response rate (ORR)(From time of informed consent and up to three years after final patient is enrolled)
- Overall Survival (OS)(From time of informed consent and up to three years after final patient is enrolled)