A Phase 1 Study of DS-3201b in Subjects With Acute Myelogenous Leukemia (AML) or Acute Lymphocytic Leukemia (ALL)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 28
- 试验地点
- 6
- 主要终点
- Number of Participants With Any Grade Treatment-emergent Adverse Event Classified as Dose-limiting Toxicities (Dose Escalation)
研究概览
简要总结
This research study tests an investigational drug called DS-3201b. An investigational drug is a medication that is still being studied and has not yet been approved by the United States Food and Drug Administration (FDA). The FDA allows DS-3201b to be used only in research. It is not known if DS-3201b will work or not.
This study consists of two parts. The first part (Part 1) is a dose escalation that will enroll subjects with AML or ALL that did not respond or no longer respond to previous standard therapy. The purpose of Part 1 of this research study is to determine the highest dose a patient can tolerate or recommended dose of DS-3201b that can be given to subjects with AML or ALL. Once the highest tolerable dose is determined, additional subjects will be enrolled at that dose into Part 2 of the study.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has AML or ALL and failed any prior induction therapy regimen or have relapsed after prior therapy
- •Has Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Has adequate renal and hepatic function
- •Had at least 14 days for prior treatment to clear the body before initiation of DS-3201b administration (except for hydroxyurea that needs only 2 days for clearance)
- •Able to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or comorbidity that would interfere with therapy.
- •Agrees to use an adequate method of contraception during the study and until 3 months after the last treatment.
- •Is willing to provide bone marrow biopsies and comply with protocol-defined evaluations
- •Has a life expectancy of at least 3 months
排除标准
- •Has presence of central nervous system (CNS) involvement of leukemia or a history of CNS leukemia
- •Has a second concurrent active primary malignancy such as solid tumor or lymphoma under active treatment
- •Has refractory nausea and vomiting, malabsorption, biliary shunt, significant bowel resection, graft versus- host disease (GVHD) significantly affecting gut motility or absorption, or any other condition that would preclude adequate absorption of DS- 3201b in the opinion of the treating physician and/or principal investigator (PI)
- •Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or tested positive for active hepatitis B or C infection
- •Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator or Sponsor
- •Has unresolved toxicities from previous anticancer therapy
- •Has received hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of DS-3201b
- •Has received concomitant treatment with a strong inhibitor or inducer of cytochrome P450 (CYP)3A4/5 within 7 days of first receipt of DS-3201b
- •Has consumed herbs/fruits that may have an influence on pharmacokinetics (PK) of DS-3201b from 3 days (14 days for St. John's wort) prior to the start of the study and throughout the entire study
- •Had major surgery within 4 weeks before study drug treatment
- •Has prolonged corrected QT interval by Fridericia's method (QTcF) at rest, where the mean QTcF interval is > 450 milliseconds (ms) based on triplicate electrocardiograms (ECGs)
- •Is pregnant or breastfeeding
- •Has substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the subject's participation in the clinical study or evaluation of the clinical study results
- •Has received prior treatment with enhancer of zeste homolog (EZH) inhibitor
研究组 & 干预措施
DS-3201b 100 mg
Participants who received 100 mg DS-3201b administered orally to participants with AML or ALL.
干预措施: DS-3201b (Drug)
DS-3201b 150 mg
Participants who received 150 mg DS-3201b administered orally to participants with AML or ALL.
干预措施: DS-3201b (Drug)
DS-3201b 250 mg
Participants who received 250 mg DS-3201b administered orally to participants with AML or ALL.
干预措施: DS-3201b (Drug)
DS-3201b 500 mg
Participants who received 500 mg DS-3201b administered orally to participants with AML or ALL.
干预措施: DS-3201b (Drug)
DS-3201b 700 mg
Participants who received 700 mg DS-3201b administered orally to participants with AML or ALL.
干预措施: DS-3201b (Drug)
结局指标
主要结局
Number of Participants With Any Grade Treatment-emergent Adverse Event Classified as Dose-limiting Toxicities (Dose Escalation)
时间窗: Baseline up to Day 28
Dose-limiting toxicity (DLT) is defined as a clinically significant non-hematologic treatment-emergent adverse event (TEAE) or abnormal clinical laboratory value that is clearly not related to disease progression, intercurrent illness, and occurring during the first cycle (28 days) on study that meets any of the following criteria: National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Grade 3 aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), or bilirubin for ≥7 days; NCI-CTCAE Grade 4 AST (SGOT) or ALT (SGPT) of any duration; All Grade 4 non-hematologic toxicities of any duration; Any Grade 5 toxicity, unless proven to be clearly and incontrovertibly related to disease progression or intercurrent illness will constitute a DLT; All other clinically significant, non-hematological NCI-CTCAE Grade 3/4 AEs. AEs were coded using the MedDRA dictionary, Version 23.0.
Number of Participants Who Experienced Any Grade Treatment-emergent Adverse Event (Dose Escalation)
时间窗: Baseline up to 30 days after last study dose, up to approximately 4 years
A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that occurs, having been absent before the first dose of study drug or has worsened after initiating the study drug until 30 days after the last dose of the study drug. AEs were coded using the MedDRA dictionary, Version 23.0.
次要结局
- Pharmacokinetic Parameter Maximum (Peak) Observed Concentration (Cmax) of DS-3201b(Cycle 1 Days 1 and 8 predose, 0.5, 1, 2, 4, 6, and 8 hours and Cycle 1 Day 15 postdose (each cycle is 28 days))
- Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of DS-3201b(Cycle 1 Day 2 postdose (each cycle is 28 days))
- Pharmacokinetic Parameter Area Under Plasma Concentration-Time Curve of DS-3201b(Cycle 1 Days 1 and 8 predose, 0.5, 1, 2, 4, 6, and 8 hours and Cycle 1 Day 15 postdose (each cycle is 28 days))
- Pharmacokinetic Parameter Time to Maximum Observed Concentration (Tmax) of DS-3201b(Cycle 1 Days 1 and 8 predose, 0.5, 1, 2, 4, 6, and 8 hours and Cycle 1 Day 15 postdose (each cycle is 28 days))