NCT05360160招募中1 期
A Phase I-II Study Investigating the All Oral Combination of the Menin Inhibitor SNDX-5613 With Decitabine/Cedazuridine (ASTX727) and Venetoclax in Acute Myeloid Leukemia (SAVE)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- To establish the recommended phase II dose (RP2D) of SNDX-5613 in combination with oral decitabine/cedazuridine (ASTX727) and venetoclax for patients with acute myeloid leukemia (AML).
研究概览
简要总结
Part 1b of this clinical research study is to find the highest tolerable dose of SNDX-5613 that can be given in combination with ASTX727 (a combination of the drugs decitabine/cedazuridine) and venetoclax for patients with acute myeloid leukemia (AML) or those with a mixed phenotype acute leukemia with a myeloid phenotype (MPAL).
Part 2 of this study is to learn if the dose of study drugs found in Part 1b can help to control AML/MPAL
详细描述
Primary Objectives:
Phase Ib
• To determine the safety, tolerability and recommended phase II dose (RP2D) of SNDX-5613 in combination with oral decitabine/cedazuridine (ASTX727) and venetoclax for patients with acute myeloid leukemia (AML).
Phase II
• To assess the efficacy of SNDX-5613 in combination with ASTX727 and venetoclax for patients with AML.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 12 years with weight ≥ 40Kg.
- •ECOG performance status of ≤
- •Newly diagnosed (frontline cohort), who are not eligible for high-intensity induction chemotherapy or relapsed/refractory (R/R cohort) AML or myeloid phenotype MPAL with either KMT2Ar, or NUP98r, or NPM1c.
- •WBC must be below 25,000/ μL at time of enrollment. Patients may receive cytoreduction prior to enrollment.
- •Baseline ejection fraction must be > 40%.
- •Adequate hepatic function (direct bilirubin < 2x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT < 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT < 5x ULN will be considered eligible).
- •Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to disease.
- •Willing and able to provide informed consent.
- •In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
- •Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study and at least 3 months after the last treatment.
排除标准
- •Prior treatment with a menin inhibitor.
- •Patients with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.
- •The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for patients with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.
- •Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
- •Patients with a concurrent active malignancy under treatment.
- •Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
- •Female subjects who are pregnant or breast-feeding.
- •Patient has an active uncontrolled infection.
- •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.
- •QTc >470 msec using the Fridericia Formula.
- •History of a complete bundle branch block or high-degree atrioventricular block.
- •History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate.
- •Clinically active central nervous system (CNS) leukemia.
- •Patients on immunosuppressive therapy post-HSCT at the time of screening with R/R leukemia (must be off all systemic immunosuppression therapy for at least 2 weeks and calcineurin inhibitors for at least 4 weeks). The use of topical steroids for cutaneous graftversus- host disease (GVHD) or stable systemic steroid doses less than or equal to 20 mg of prednisone daily are permitted.
- •Patients with Grade > 2 active acute GVHD, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
研究组 & 干预措施
SNDX-5613
Experimental
Capsules by mouth 2 times every day (about 12 hours apart).
干预措施: SNDX-5613 (Drug)
Venetoclax
Experimental
Tablets by mouth on Days 1-14 of each cycle.
干预措施: Venetoclax (Drug)
ASTX727
Experimental
Tablets by mouth on Days 1-5 of each cycle.
干预措施: ASTX727 (Drug)
结局指标
主要结局
To establish the recommended phase II dose (RP2D) of SNDX-5613 in combination with oral decitabine/cedazuridine (ASTX727) and venetoclax for patients with acute myeloid leukemia (AML).
时间窗: through study completion, an average of 1 year
次要结局
未报告次要终点
研究者
研究点 (1)
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相关资讯
Revumenib Combination Shows Promise in Relapsed/Refractory AML with Specific Genetic Alterations- The phase 1/2 SAVE study evaluated an all-oral combination of revumenib, decitabine/cedazuridine, and venetoclax in relapsed/refractory AML patients.
- The overall response rate was 82%, with notable efficacy in patients harboring _KMT2Ar_ (88%), _NPM1mt_ (67%), and _NUP98r_ (100%) genetic alterations.
- A significant proportion of responders achieved minimal residual disease (MRD) negativity, particularly those with complete remission or complete remission with partial hematologic recovery.
- The combination demonstrated a manageable safety profile, with common grade 3 or higher adverse events including febrile neutropenia and lung infection.last yearFDA Approves Revumenib for Relapsed/Refractory KMT2A-Rearranged Acute Leukemia- The FDA has approved revumenib (Revuforj; Syndax Pharmaceuticals) as a first-in-class therapy for relapsed or refractory acute leukemia with KMT2A rearrangements.
- Revumenib, a menin inhibitor, targets the interaction between menin and KMT2A protein, which is crucial for the leukemogenic process in KMT2Ar leukemia.
- Clinical trials showed revumenib significantly improved remission rates compared to historical controls, with a complete remission rate of 22.8% in the AUGMENT-101 trial.
- Pharmacists play a vital role in optimizing dosing, monitoring for adverse events like QTc prolongation and differentiation syndrome, and ensuring patient safety.last year