Phase 1 Study of KHK2823 in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 39
- 试验地点
- 7
- 主要终点
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
研究概览
简要总结
This is a first in human, non-randomized, open-label, dose escalation study to investigate the safety, pharmacokinetics, immunogenicity and pharmacodynamics of repeat doses of KHK2823.
详细描述
This is a Phase 1, multi-center, open-label, dose-escalation study of KHK2823 in adult patients with previously untreated AML who are not candidates for intensive remission induction therapy; relapsed/refractory AML for whom no other standard therapy is available or appropriate; or relapsed/refractory MDS who have received prior therapy with a hypomethylating agent, such as decitabine and azacitidine or who are not candidates to receive a hypomethylating agent, this would include high risk or transfusion-dependent low risk patients. Patients must have documented primary or secondary AML or MDS according to World Health Organization (WHO) criteria. Following the provision of signed informed consent, patients will be screened for entry into the study. The study consists of 2 parts. In Part 1, 3 to 6 patients per cohort will be enrolled sequentially in up to 7 dose-escalation cohorts to establish the MTD. KHK2823 will be administered once weekly. In Part 2, up to an additional 18 patients may be enrolled to further evaluate the safety, PK, PD, potential anti-leukemic activity of KHK2823.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Males and females ≥ 18 years old with previously untreated AML who are not candidates for intensive remission induction therapy; relapsed/refractory AML for whom no other standard therapy is available or appropriate; or relapsed/refractory MDS who have received prior therapy with a hypomethylating agent or who are not candidates to receive a hypomethylating agent
- •Histopathologically/cytologically documented primary or secondary AML, as defined by WHO criteria, or MDS, confirmed by pathology review at treating institution
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
- •Life expectancy of at least 3 months
排除标准
- •Histological diagnosis of acute promyelocytic leukemia (FAB Type M3)
- •Clinically significant central nervous system leukemia
- •Treatment of the underlying hematologic condition with systemic therapy during the treatment period, including any chemotherapy, radiation or investigational therapy, within 2 weeks prior to KHK2823 administration; or immunotherapy within 30 days prior to KHK2823 administration; with the exception of hydroxyurea (Hydrea®) for treatment of hyperleukocytosis, which must be discontinued at least 24 hours prior to the first dose of KHK2823
研究组 & 干预措施
KHK2823
single agent KHK2823 administered at selected dose levels
干预措施: KHK2823 (Drug)
结局指标
主要结局
Number of Participants with Adverse Events as a Measure of Safety and Tolerability.
时间窗: Assessed weekly for duration of treatment (anticipated minimum 8 weeks), plus 42 day follow up period
次要结局
- Pharmacokinetics: Peak serum concentration (Cmax) Time to reach Cmax (tmax) Minimum serum concentration (Ctrough) Area under curve (AUC) Half-life (t1/2) Clearance (CL) Volume of distribution (Vd) Accumulation ratio (R)(Assessed during first 24 weeks of treatment, plus 42 day follow up period)
- Disease Response: overall response rate (ORR), overall survival (OS), event-free survival (EFS), relapse-free survival (RFS), progression-free survival (PFS) and disease-free survival (DFS)(Assessed every 8 weeks for duration of treatment (anticipated minimum 8 weeks), plus 14 day follow up period)
- Immunogenicity: anti-KHK2823 antibody(Assessed every 4 weeks for first 24 weeks of treatment, plus 42 day follow up period)
- Pharmacodynamics: CD123+(Assessed during first 24 weeks of treatment, plus 42 day follow up period)