A Phase 1, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate Safety, Tolerability, and Clinical Activity of SNDX-5613 in Combination With Intensive Chemotherapy in Participants With Newly Diagnosed Acute Myeloid Leukemias Harboring Alterations in Lysine-specific Methyltransferase 2A (KMT2A/MLL), Nucleophosmin 1 (NPM1), and Nucleoporin 98 (NUP98) Genes
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 76
- 试验地点
- 54
- 主要终点
- Number of Participants with Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of SNDX-5613 in combination with intensive chemotherapy in participants with newly diagnosed acute myeloid leukemia (AML) harboring alterations in KMT2A, NPM1, or NUP98 genes.
详细描述
The Dose Escalation portion of this study will identify the maximum tolerated dose, or if different, the recommended Phase 2 dose of SNDX-5613 to be used in combination with intensive chemotherapy and in maintenance monotherapy following intensive chemotherapy in participants with newly diagnosed AML harboring alterations in KMT2A, NPM1, or NUP98 genes.
In the Dose Expansion portion of the study, safety and preliminary efficacy of SNDX-5613 may be explored in expansion cohorts at tolerated dose levels.
In both Dose Escalation and Dose Expansion, the treatment period will consist of an induction phase (up to 2 cycles), a consolidation phase (up to 4 cycles and could include hematopoietic stem cell transplant for participants who are transplant eligible and have an available donor), and a maintenance monotherapy phase with SNDX-5613. The cycle duration will be 28 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Established, pathologically confirmed diagnosis of AML by World Health Organization 2022 criteria.
- •Previously untreated AML and eligible to receive intensive chemotherapy.
- •KMT2Ar, NPM1c, or NUP98r mutations identified by local laboratory prior to the first dose of SNDX-
- •Eastern Cooperative Oncology Group performance status ≤2 and ≤1 if >65 years old .
- •Adequate liver, kidney, and cardiac function.
排除标准
- •Diagnosis of acute promyelocytic leukemia.
- •Clinically active central nervous system leukemia (blasts detected in cerebrospinal fluid, radiographic or clinical signs and symptoms).
- •Fridericia's corrected QT interval (QTcF) >450 milliseconds (average of triplicate), diagnosis or suspicion of Long QT syndrome or family history of Long QT syndrome.
- •Any gastrointestinal issue of the upper gastrointestinal tract that might affect oral drug absorption or ingestion.
- •Cirrhosis with a Child-Pugh score of B or C.
- •Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
- •Hepatitis B, Hepatitis C, or HIV-positive with detectable viral load.
- •Documented active, uncontrolled infection.
- •Uncontrolled disseminated intravascular coagulation.
- •Lactating/breast feeding or pregnant.
- •Use of prohibited concomitant chemotherapy, radiation therapy, or immunotherapy.
- •Use of strong CYP3A4 inducers or inhibitors (except for Itraconazole, Ketoconazole, Posaconazole, or Voriconazole).
研究组 & 干预措施
SNDX-5613
Dose Escalation:
- Induction: Sequential cohorts of escalating dose levels of SNDX-5613 with chemotherapy regimen.
- Consolidation: Cohorts will receive high-dose cytarabine (HiDAC) chemotherapy followed by SNDX-5613.
- Maintenance Monotherapy: Cohorts will receive SNDX-5613.
Dose Expansion:
- Induction: SNDX-5613 at tolerated dose level with chemotherapy regimen.
- Consolidation: Cohorts will receive SNDX-5613 with chemotherapy regimen and HiDAC.
- Maintenance Monotherapy: Cohorts will receive SNDX-5613.
干预措施: SNDX-5613 (Drug)
SNDX-5613
Dose Escalation:
- Induction: Sequential cohorts of escalating dose levels of SNDX-5613 with chemotherapy regimen.
- Consolidation: Cohorts will receive high-dose cytarabine (HiDAC) chemotherapy followed by SNDX-5613.
- Maintenance Monotherapy: Cohorts will receive SNDX-5613.
Dose Expansion:
- Induction: SNDX-5613 at tolerated dose level with chemotherapy regimen.
- Consolidation: Cohorts will receive SNDX-5613 with chemotherapy regimen and HiDAC.
- Maintenance Monotherapy: Cohorts will receive SNDX-5613.
干预措施: Chemotherapy Regimen (Drug)
SNDX-5613
Dose Escalation:
- Induction: Sequential cohorts of escalating dose levels of SNDX-5613 with chemotherapy regimen.
- Consolidation: Cohorts will receive high-dose cytarabine (HiDAC) chemotherapy followed by SNDX-5613.
- Maintenance Monotherapy: Cohorts will receive SNDX-5613.
Dose Expansion:
- Induction: SNDX-5613 at tolerated dose level with chemotherapy regimen.
- Consolidation: Cohorts will receive SNDX-5613 with chemotherapy regimen and HiDAC.
- Maintenance Monotherapy: Cohorts will receive SNDX-5613.
干预措施: HiDAC (Drug)
结局指标
主要结局
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: Day 1 through 30 days after final dose (up to approximately 3 years)
Dose Escalation: Number of Participants with Dose-limiting Toxicities
时间窗: Up to Day 42
次要结局
- Maximum Plasma Concentration (Cmax) of SNDX-5613 and Relevant Metabolites(Predose through Day 15)
- Area Under the Plasma Concentration Versus Time Curve From Time 0 to t (AUC0-t) of SNDX-5613 and Relevant Metabolites(Predose through Day 15)
研究者
Jessica Clement
Scientific
Syndax Pharmaceuticals Inc.