A Phase 1/2, Multicenter, First-in-Human, Dose Escalation and Expansion Study Evaluating CHM-029 as Monotherapy in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) With NPM1 Mutations, KMT2A or NUP98 Rearrangements
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Number of participants with dose limiting toxicities (DLTs)
研究概览
简要总结
The goal of this study is to evaluate the safety of CHM-029, an investigational oral medicine, and to evaluate its activity in treating certain types of acute myeloid leukemia (AML) in adults. The main questions the study aims to answer are:
- What is an appropriate dose of CHM-029?
- What side effects may occur with CHM-029?
- How does the body process CHM-029?
Researchers will evaluate increasing dose levels of CHM-029 to better understand its safety and how the body responds to treatment.
Participants will visit the study clinic regularly for safety assessments, blood tests, electrocardiograms (ECGs), and bone marrow evaluations to monitor their health and response to treatment.
详细描述
CHM-029-01 is a Phase 1/2, first-in-human, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antileukemic activity of orally administered CHM-029 in adults with relapsed or refractory acute myeloid leukemia (AML) with an NPM1 mutation, KMT2A rearrangement, or NUP98 rearrangement.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •18 years old and above
- •Relapsed or refractory (R/R) acute myeloid leukemia (AML) and has had treatment with any available standard therapies
- •Positive for NPM1 mutation, or KMT2A or NUP98 rearrangements
排除标准
- •White blood cell (WBC) count higher than 25,000 u/L that cannot be maintained below threshold with hydroxyurea treatment
- •Extramedullary only AML
- •Has current complications related to hematopoietic stem cell transplant (HSCT)
- •Other cancers that require treatment
- •Active Hepatitis or HIV infection
- •Moderate hepatic or renal impairment
- •Acute promyelocytic leukemia
- •Baseline prolongation of QT/QTc interval (≥ 470 ms) or additional risk factors for Torsades de Pointes (TdP)
- •Congestive heart failure NYHA Class 3 or 4
- •Central nervous system involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation
研究组 & 干预措施
CHM-029 Dose Escalation
Participants will receive CHM-029 orally. Dose levels will be escalated based on dose limiting toxicities (DLTs) as evaluated by the Safety Review Committee (SRC).
干预措施: CHM-029 (Drug)
CHM-029 Backfill
Participants will receive CHM-029 orally at a dose level already evaluated by the Safety Review Committee (SRC).
干预措施: CHM-029 (Drug)
结局指标
主要结局
Number of participants with dose limiting toxicities (DLTs)
时间窗: Baseline through Day 28
A DLT is defined as any Adverse Event (AE) which meets DLT criteria, not clearly due to the underlying disease or extraneous causes, that occurs within the DLT observation period.
Number of participants with adverse events (AEs)
时间窗: Baseline through study completion, an average of 3 years
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of participants with adverse events (AEs) by severity
时间窗: Baseline through study completion, an average of 3 years
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 6.0
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
时间窗: Baseline through study completion, an average of 3 years
Number of participants with potentially clinically significant laboratory values.
Rates of dose modification due to adverse events (AEs) according to NCI CTCAE
时间窗: Baseline through study completion, an average of 3 years
Safety and tolerability will be evaluated by dose interruption, modification, and discontinuation due to adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.6.0
Maximum tolerated dose (MTD) and/or optimal biological dose (OBD) of CHM-029
时间窗: Baseline through study completion, an average of 3 years
Maximum tolerated dose or optimal biological dose will be determined by the sponsor based on the Safety Review Committee's recommendation considering the totality of the available clinical safety, clinical efficacy, pharmacokinetics (PK), and pharmacodynamic data
次要结局
- Pharmacokinetics (PK) profile of CHM-029: Plasma concentrations(Baseline through study completion, an average of 3 years)
- Pharmacokinetic (PK) profile of CHM-029: Area under the curve(Baseline through study completion, an average of 3 years)
- Pharmacokinetic (PK) profile of CHM-029: Time of maximum concentration (Tmax) and half-life (T1/2)(Baseline through study completion, an average of 3 years)
- Complete remission and complete remission with partial hematological recovery (CR/CRh) rate(Baseline to study completion, an average of 3 years)
- Composite complete remission rate (CRc)(Baseline through study completion, an average of 3 years)
- Duration of response (DOR)(Baseline through study completion, an average of 3 years)
- Morphological leukemia free state (MLFS) rate(Baseline through study completion, an average of 3 years)
- Best response rate(Baseline through study completion, an average of 3 years)
- Overall survival (OS)(Baseline through study completion, an average of 3 years)
- Event free survival (EFS)(Baseline through study completion, an average of 3 years)