A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Occurrence of adverse events (AEs)
研究概览
简要总结
To assess safety and tolerability, describe the dose-limiting toxicities, determine the maximum tolerated dose (MTD) or the highest protocol-defined dose (maximum administered dose) in the absence of establishing the MTD, and a recommended dose for further evaluation of MEDI7247 in patients with selected hematological malignancies who have relapsed after, or are refractory to prior standard therapy, and for whom there is no standard salvage regimen available.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed relapsed/refractory diagnosis of select hematologic malignancies for which no standard/salvage therapies are available.
- •Age ≥ 18 years at the time of screening.
- •Written informed consent and any locally required authorization
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Liver Function Tests: AST and ALT ≤ 3 × ULN, and serum TBL ≤ 1.5 × ULN, unless consistent with Gilbert's syndrome for which TBL ≤ 2.5 × ULN is allowed.
- •CrCL ≥ 40 mL/min
- •Female patients of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from 7 days post-screening, and must agree to continue using such precautions for 90 days after the last dose of investigational product.
- •Nonsterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from 7 days post-screening and for 90 days after receipt of the last dose of investigational product.
排除标准
- •Received cytotoxic chemotherapy within 21 days (or 42 days for nitrosureas or mitomycin C) prior to the first scheduled dose of MEDI
- •Received major surgery (as defined by the Investigator), radiotherapy, or immunotherapy (including immune checkpoint inhibitors and adoptive cellular therapy such as autologous or donor NK cell or T lymphocyte infusions (e.g. CAR -T cells)) within 28 days of the first scheduled dose of MEDI
- •Received an investigational drug within 14 days of the first scheduled dose of MEDI7247 or not recovered from associated toxicities.
- •Patients who have previously received an autologous SCT, are excluded if less than 120 days have elapsed from the time of transplant or the patient has not recovered from transplant-associated toxicities prior to the first scheduled dose of MEDI
- •History of liver cirrhosis, liver fibrosis or prior liver irradiation regardless of the time interval (not including total body irradiation administered during allogeneic SCT).
- •Failure to recover from all prior treatment-related non-hematological toxicities to ≤ Grade 1 prior to the first scheduled dose of MEDI7247 (except for alopecia and neuropathy).
- •Patients at risk of non-disease related major bleeding (eg, recent GI hemorrhage or neurosurgery, within previous 21 days).
- •Current severe active systemic disease including active concurrent malignancy
- •Central nervous system (CNS) disease that is untreated, symptomatic, or requires therapy to control symptoms.
- •Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infections at the time of screening.
研究组 & 干预措施
acute myeloid leukemia
Patients with R/R AML by World Health Organization (WHO) classification (Arber et al, 2016) who have failed prior standard therapy and for whom no standard therapies are available
干预措施: MEDI7247 (Drug)
Multiple Myeloma
Patients with R/R MM who have failed prior standard therapy(ies) which should include immunomodulatory agents and proteasome inhibitors and for whom there is no standard salvage regimen.
干预措施: MEDI7247 (Drug)
Diffuse Large B-cell Lymphoma
Patients with R/R DLBCL who have failed prior standard therapy(ies) and for whom there is no standard salvage regimen.
干预措施: MEDI7247 (Drug)
结局指标
主要结局
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)
Occurrence of serious adverse events (SAEs)
时间窗: From time of informed consent through 90 days post end of treatment
To assess by the occurrence of serious adverse events (SAEs)
Occurrence of dose-limiting toxicities (DLTs)
时间窗: During the evaluation period of 21 or 42 days post-first dose
To assess by the occurrence of non-Hematologic and hematologic toxicities, AEs, and abnormal laboratory results.
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 urinalysis
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 electrocardiogram (ECG) results from baseline
时间窗: From time of informed consent and up to 21 days post end of treatment
To assess using twelve-lead ECG recordings
Percentage 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 urinalysis
次要结局
- MEDI7247 area under the concentration-time curve for PK(From time of informed consent through 30 days post end of treatment)
- Objective response rate (ORR)(From time of informed consent and up to 3 years after final patient is enrolled)
- Progression-free survival (PFS)(From time of informed consent and up to 3 years after final patient is enrolled)
- MEDI7247 maximum observed concentration for PK(From time of informed consent through 30 days post end of treatment)
- Time to response (TTR)(From time of informed consent and up to 3 years after final patient is enrolled)
- MEDI7247 clearance for PK(From time of informed consent through 30 days post end of treatment)
- MEDI7247 terminal half-life for PK(From time of informed consent through 30 days post end of treatment)
- Best overall response (BOR)(From time of informed consent and up to 3 years after final patient is enrolled)
- Duration of response (DoR)(From time of informed consent and up to 3 years after final patient is enrolled)
- Number of subjects who develop anti-drug antibodies (ADAs)(From time of informed consent through 30 days post end of treatment)
- Overall survival (OS)(From time of informed consent and up to 3 years after final patient is enrolled)