Phase 2 Study to Assess the Safety and Efficacy of Bomedemstat (IMG-7289) in Combination With Ruxolitinib in Patients With Myelofibrosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
This is an open-label, Phase 2 study of bomedemstat (IMG-7289), an inhibitor of lysine-specific demethylase 1 (LSD1), in combination with JAK inhibition (JAKi) in patients with myelofibrosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Patients refractory to, relapsed or intolerant of ruxolitinib as per one of the below:
- •Refractory is defined as <30% reduction in spleen length or <10% SVR compared to baseline having received ruxolitinib for ≥12 weeks prior to enrollment, AND on a stable dose for ≥8 weeks prior to starting investigational therapy
- •Relapsed is defined as an increase in spleen volume of ≥25% by MRI/CT from nadir, or, ≥100% in palpable spleen length from a baseline of 5 to 10 cm BLCM or, ≥50% increase in spleen length from a baseline spleen length ≥10 cm BLCM
- •Intolerance is defined as the development in patients treated with ruxolitinib for ≥28 days of:
- •Red blood cell transfusion requirement of 2 units/month for 2 months
- •Grade 3 thrombocytopenia, anemia, hematoma, and/or hemorrhage while on ruxolitinib treatment
- •Patients who are JAK inhibitor naïve, AND:
- •Require MF-directed treatment, AND
- •Have measurable disease burden including one of the following:
- •Disease-related symptoms, determined by a MFSAF or MPN-SAF TSS of ≥10, or at least 2 symptoms with scores ≥3
- •Documented splenomegaly by physical exam, with spleen palpated ≥5 cm below the left costal margin
- •Both Cohorts A and B:
- •Willing and able to provide informed consent
- •Age ≥18 years
- •Diagnosis of Overt Myelofibrosis (primary, post-ET, or post-PV) per World Health Organization (WHO) diagnostic criteria
- •Intermediate-1, Intermediate-2, or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Platelet count ≥100 x 10^9/L prior to dosing on Cycle 1 Day 1
- •Absolute neutrophil count ≥0.5 x 10^9/L prior to dosing on Cycle 1 Day 1
- •Peripheral blast count ≤10% prior to dosing on Cycle 1 Day 1
- •Able to swallow capsules
- •Women of childbearing potential and fertile men must agree to use an approved method of contraception from Screening until 30 days after the last dose of bomedemstat and ruxolitinib.
排除标准
- •Those with increased risk of bleeding, including any of the following:
- •Activated partial thromboplastin time (aPTT) ≥1.3 x the local upper limit of normal
- •International normalized ratio (INR) ≥1.3 x the local upper limit of normal
- •Known history of a platelet function disorder
- •Other known bleeding disorder that is active at the time of screening (Von Willebrand's disease, dysfibrinogenemia, hemophilia, etc.)
- •History of splenectomy or prior splenic irradiation
- •Use of an investigational agent within 14 days of study treatment (or at least 7 half-lives of that agent, whichever is longer), prior to the first dose of bomedemstat
- •Current use of monoamine oxidase A and B inhibitors (MAOIs)
- •Uncontrolled, active infection
- •Major surgery within 4 weeks of starting the study drug, or not recovered from side effects of surgery
- •Any other serious medical conditions that could compromise study participation, in the opinion of the investigator
- •Known HIV infection or known, active hepatitis B or hepatitis C infection
- •Concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, i.e., non-melanoma skin cancers, are eligible)
- •Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bomedemstat or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates participation
- •Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to hemolysis) as defined by any of the following local lab parameters:
- •Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) <40 mL/min or serum creatinine >1.5 x the local upper limit of normal
- •Aspartate transaminase (AST) or alanine aminotransferase (ALT) ≥2.5 x the local upper limit of normal
- •Pregnant or lactating females, or females planning to become pregnant at any time during the study
- •Unwilling or unable to comply with the study protocol
研究组 & 干预措施
Cohort A (Patients refractory to, relapsed or intolerant of ruxolitinib):
Bomedemstat : The starting dose of bomedemstat at Initial Treatment Period Cycle 1 Day 1 will be 0.4 mg/kg daily for all patients in Cohort A. The first up-titration is not permitted until Initial Treatment Period Cycle 2 Day 1; thereafter, the dose may be up-titrated no more frequently than every 4 weeks from the prior up- or down-titration (note: down-titrations may occur at any time (or the current dose maintained) in the best interest and safety of the patient), to a target platelet count range of 50-100 x 10^9/L.
Ruxolitinib: Patients will continue their prior, stable dose of ruxolitinib. This same dose will be continued throughout the study unless dose modification is required because of toxicity.
干预措施: Bomedemstat (Drug)
Cohort B (Cohort B will consist of 10 patients who are JAK inhibitor naïve):
Bomedemstat: The starting dose of bomedemstat at Initial Treatment Period Cycle 1 Day 1 will be 0.4 mg/kg daily for all patients in Cohort B. The first up-titration is not permitted until Initial Treatment Period Cycle 2 Day 1; thereafter, the dose may be up-titrated no more frequently than every 4 weeks from the prior up- or down-titration (note: down-titrations may occur at any time (or the current dose maintained) in the best interest and safety of the patient), to a target platelet count range of 50-100 x 10^9/L.
Ruxolitinib: Patients will start treatment with ruxolitinib at Initial Treatment Period Cycle 1 Day 1. The starting dose of ruxolitinib will be 10 mg BID. This same dose will be continued throughout the study unless dose modification is required because of toxicity.
干预措施: Bomedemstat (Drug)
结局指标
主要结局
Adverse events
时间窗: 24 months
Enumeration and description of adverse events (AEs), including determination of dose limiting toxicities (DLTs), serious adverse events (SAEs), and other AEs
次要结局
- Spleen response at 24 weeks(24 weeks)
- Symptom response at 24 weeks(24 weeks)