A Phase 1 Trial of Indoximod in Combination With Idarubicin and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 2
- 主要终点
- Safety assessed by development of RLT, AEs and laboratory parameters of indoximod.
研究概览
简要总结
The purpose of this study is to characterize the regimen limiting toxicities (RLT) and recommended Phase 2 dose (RP2D) of indoximod in patients with newly diagnosed AML receiving remission induction chemotherapy with cytarabine and idarubicin.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A histologically or pathologically confirmed diagnosis of AML based on WHO classification with or without extramedullary disease except for central nervous system disease.
- •ECOG performance status ≤ 2
- •Left ventricular ejection fraction (LVEF) ≥ 50%
- •Female patients of childbearing potential must have a negative pregnancy test < 1 week prior to enrollment.
- •Ability to understand and willingness to sign a written informed consent document.
排除标准
- •Patients receiving any other investigational agents or immunotherapy
- •Patients who have received prior chemotherapy for AML with the exception of hydroxyurea or leukapheresis for leukocytosis; prior hypomethylating or immunomodulatory agents for MDS are allowed
- •Previous allo-HSCT of any kind
- •Active, uncontrolled infection including known hepatitis B or C
- •Active autoimmune disease and chronic inflammatory conditions requiring concurrent use of any systemic immunosuppressants or steroids.
- •History of any other active cancer diagnosis
- •Pregnant women
- •Known HIV-infected patients
研究组 & 干预措施
Phase 1a
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (freebase formulation). These patients will additionally receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels.
All current subjects will transition from indoximod freebase capsules over to indoximod HCL F2 tablets. All new subjects enrolled will also receive indoximod HCL F2 tablets.
干预措施: Idarubicin (Drug)
Phase 1a
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (freebase formulation). These patients will additionally receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels.
All current subjects will transition from indoximod freebase capsules over to indoximod HCL F2 tablets. All new subjects enrolled will also receive indoximod HCL F2 tablets.
干预措施: Cytarabine (Drug)
Phase 1a
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (freebase formulation). These patients will additionally receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels.
All current subjects will transition from indoximod freebase capsules over to indoximod HCL F2 tablets. All new subjects enrolled will also receive indoximod HCL F2 tablets.
干预措施: Indoximod Freebase (Drug)
Phase 1a
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (freebase formulation). These patients will additionally receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels.
All current subjects will transition from indoximod freebase capsules over to indoximod HCL F2 tablets. All new subjects enrolled will also receive indoximod HCL F2 tablets.
干预措施: Indoximod HCL F2 (Drug)
Phase 1b (CLOSED TO ACCRUAL)
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (HCL F1 formulation). These patients will receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels.
干预措施: Idarubicin (Drug)
Phase 1b (CLOSED TO ACCRUAL)
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (HCL F1 formulation). These patients will receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels.
干预措施: Cytarabine (Drug)
Phase 1b (CLOSED TO ACCRUAL)
Patients enrolled in this arm will receive standard induction and consolidation chemotherapy (7+3) with Indoximod (HCL F1 formulation). These patients will receive maintenance therapy with indoximod for 6 months after consolidation therapy. The indoximod dose will be studied in up to 4 dose levels.
干预措施: Indoximod HCL F1 (Drug)
结局指标
主要结局
Safety assessed by development of RLT, AEs and laboratory parameters of indoximod.
时间窗: 6 months
Phase 1
Comparison of serum concentrations (Cmax/Steady State) of indoximod freebase and indoximod salt formulation.
时间窗: 6 months
Phase 1
次要结局
- Clinical response rate(2 years)
- Duration of complete response(2 years)
- Event free survival(2 years)
- Cumulative incidence of relapse (CIR)(2 years)
- Overall survival (OS)(2 years)
- Measurable Residual Disease Rate(2 years)
- Proportion of AML patients who become eligible for bone marrow transplantation(2 years)
- Frequency and severity of adverse events(2 years)
- Pharmacokinetics: Serum concentrations (Cmax/Steady State)(6 months)