Ph 1b Dose Escalation Study of OXi4503 as a Single Agent and in Combination With Cytarabine With Subsequent Phase 2 Cohorts for Subjects With Relapsed/Refractory Acute AML and MDS
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 105
- 试验地点
- 4
- 主要终点
- Phase 1b:MTD of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS
研究概览
简要总结
Phase 1 will investigate maximum tolerated dose of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS.
Phase 2 will investigate overall response rate of OXi4503 in combination with intermediate-dose cytarabine in 1) subjects with MDS after failure of 1 prior hypomethylating agent (Arm A) and 2) subjects with relapsed and refractory AML after treatment failure of up to 1 prior chemotherapy regimen (Arm B).
详细描述
Phase 1 dose escalation component will assess the safety, PK/PD, and preliminary efficacy of OXi4503 as a single agent in subjects with relapsed/refractory AML and MDS, and the safety and PK/PD of the combination of OXi4503 with intermediate-dose cytarabine in subjects with AML/MDS.
Phase 2 will assess the preliminary efficacy of the OXi4503+cytarabine combination in 2 cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Provide informed consent
- •≥ 18 years of age
- •Phase 1 (dose escalation) subjects must have either:
- •AML that has failed to achieve complete remission or morphologic complete remission or
- •MDS - Marrow blasts must be > 5% and disease failed at least 1 prior hypomethylating agent
- •Phase 2 (expansion) subjects must have either MDS or relapsed/refractory AML
- •Eastern Cooperative Oncology Group performance status 0, 1, or 2
- •Total bilirubin ≤ 2
- •Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times upper limit of normal (ULN)
- •Serum creatinine < 2.5 times ULN
- •Prothrombin time (PT)/international normalized ratio and (PTT) in normal range ± 25%
- •Women of child-bearing potential
- •Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods
排除标准
- •Acute promyelocytic leukemia
- •Absolute peripheral blood myeloblast count greater than 20,000/mm3
- •Uncontrolled hypertension
- •History of congenital long QT syndrome or torsades de pointes
- •Pathologic bradycardia or heart block
- •Prolonged baseline QTc
- •Hiistory of ventricular arrhythmia
- •Myocardial infarction and/or new ST elevation
- •Any history of hemorrhagic stroke
- •Symptomatic congestive heart failure
- •Major hemorrhagic event within 28 days
- •Suggestive central nervous system involvement with leukemia
- •Any open wound
- •Pregnant and nursing subjects are excluded
- •Treatment with any anticancer therapy
- •Treatment with colchicine is excluded.
- •Psychiatric disorders that would interfere with consent
研究组 & 干预措施
Phase 2 AML
OXi4503 at MTD plus cytarabine 1g/m2/day
干预措施: Phase 2 - OXi4503 + cytarabine (Drug)
Phase 2 MDS
OXi4503 at MTD plus cytarabine 1g/m2/day
干预措施: Phase 2 - OXi4503 + cytarabine (Drug)
OXi4503 dose escalation
MTD for OXi4503 will be determined
干预措施: Phase 1 - OXi4503 (Drug)
OXi4503 + cytarabine dose escalation
MTD of the combination of OXi4503 + cytarbine will be determined
干预措施: Phase 1 - OXi4503 + cytarabine (Drug)
结局指标
主要结局
Phase 1b:MTD of OXi4503 as a single agent and in combination with intermediate-dose cytarabine in subjects with relapsed/refractory AML or MDS
时间窗: 1 year
Phase 2: Overall response rate of OXi4503 in combination with intermediate-dose cytarabine in subjects with MDS after failure of 1 prior hypomethylating agent (Arm A), and subjects with relapsed and refractory AML after treatment failure of up
时间窗: 2 years
次要结局
未报告次要终点