A Phase 1a/1b Study of ELVN-001 for the Treatment of Chronic Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 74
- 主要终点
- Phase 1a: Incidence of dose limiting toxicities
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and determine the recommended dose for further clinical evaluation of ELVN-001 in patients with chronic myeloid leukemia with and without T315I mutations in patients who are relapsed, refractory or intolerant to TKIs.
详细描述
This first-in-human trial with ELVN-001 is a dose escalation study with the primary purpose to identify the recommended dose(s) for expansion (RDEs) of single agent ELVN-001 in chronic phase CML with or without T315I mutations. The safety, tolerability and pharmacokinetic profile of ELVN-001 will be assessed together with an evaluation of changes in BCR-ABL1 transcript. An understanding of the safety profile, PK and preliminary evidence of anti-CML activity will be used to inform future development of ELVN-001 in adults with CML. By virtue of its predicted pharmacological profile ELVN-001 has the potential to be tolerable and achieve a deep molecular response in patients with CML with or without T315I mutations who do not tolerate or benefit from available TKIs.
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
入排标准
- 年龄范围
- 18 Years 至 65+ years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BCR-ABL1 positive CML in chronic phase, with or without T315I mutation.
- •US: The patient has failed or is intolerant to at least one prior second-generation tyrosine kinase inhibitor (TKI) or asciminib. Rest of World: The patient has failed, is intolerant to, or not a candidate for, available therapies known to be active for treatment of their CML (country-specific criteria may vary).
- •ECOG performance status of 0 to
- •Adequate hematologic, hepatic and renal function.
- •Prior bone marrow transplant allowed if ≥ 6 months prior to the first dose of ELVN-001.
排除标准
- •Treatment with anti-cancer or anti-CML therapy within 7 days or 5 half-lives, whichever is longer.
- •History of acute tyrosine kinase inhibitor (TKI)-related pancreatitis within 6 months of study entry. Active chronic pancreatitis, or pancreatic disease due to any cause.
- •QTc >470 ms.
研究组 & 干预措施
Phase 1a Dose Escalation
ELVN-001 administered in 3+3 dose escalation
干预措施: ELVN-001 (Drug)
Phase 1b Dose Expansion (non-T315I)
ELVN-001 administered at one or more recommended dose(s) for expansion in CML without T315I mutations
干预措施: ELVN-001 (Drug)
Phase 1b expansion (T315I)
ELVN-001 administered at the recommended dose for expansion for CML with T315I mutation
干预措施: ELVN-001 (Drug)
结局指标
主要结局
Phase 1a: Incidence of dose limiting toxicities
时间窗: 28 days
DLTs will be used to support that the recommended doses for expansion are \</= MTD
Phase 1a: Incidence of adverse events (AEs)
时间窗: up to 28 days
Adverse events will be used to support that the recommended doses for expansion are likely to be tolerable
Phase 1a: Incidence of clinically significant laboratory abnormalities
时间窗: up to 28 days
Clinically significant laboratory abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
Phase 1a: Incidence of clinically significant ECG abnormalities
时间窗: up to 28 days
Clinically significant ECG abnormalities will be used to support that the recommended doses for expansion are likely to be tolerable
Phase 1b: Incidence of clinically significant laboratory abnormalities
时间窗: up to 3 years
Clinically significant ECG abnormalities will be used to support that the dose(s) evaluated in expansion is tolerable
Phase 1b: Incidence of clinically significant ECG abnormalities
时间窗: up to 3 years
Clinically significant ECG abnormalities will be used to support that the recommended dose(s) evaluated in expansion is tolerable
Phase 1b: Incidence of adverse events
时间窗: up to 3 years
Adverse events will be used to support that the dose(s) evaluated in expansion is tolerable
次要结局
- Phase 1a and 1b: area under the curve(6 months)
- Phase 1a and 1b: maximum concentration(6 months)
- Phase 1a and 1b: time of maximum concentration(6 months)
- Phase 1a and 1b: minimum concentration(6 months)
- Phase 1a and 1b: Molecular response (MR)(up to 3 years)
- Phase 1b: Duration of Molecular Response(up to 3 years)
- Phase 1b: Complete Hematologic Response (CHR)(up to 3 years)
研究者
Clinical Development Lead
Scientific
Enliven Therapeutics Inc.