NCT04262141进行中（未招募）2 期
Investigator-Initiated Trial of the LSD1 Inhibitor IMG-7289 for the Treatment of Patients With Essential Thrombocythemia (ET) or Polycythemia Vera (PV) That Have Failed at Least One Standard Therapy
Terrence J Bradley, MD1 个研究点 分布在 1 个国家目标入组 4 人开始时间: 2020年10月2日最近更新:
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Hematologic Response Rates
研究概览
简要总结
The purpose of this study is to assess the hematologic effects of IMG-7289 therapy in ET and PV patients who require platelet, White Blood Cell (WBC) or Red Blood Cell (RBC) control, and have failed at least one standard therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Age ≥ 18 years.
- •Diagnosis of Essential Thrombocythemia or Polycythemia Vera per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Arber et al., 2016).
- •Patients that have failed at least one standard therapy (failure is the equivalent of inadequate response or intolerance).
- •Platelet count >400 x 10^9/L pre-dose Day 1for patients with essential thrombocytopenia.
- •Platelet count >150 x 10^9/L pre-dose Day 1 for patients with polycythemia vera.
- •Peripheral blast count < 10% pre-dose Day
- •Absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L pre-dose Day
- •Fibrosis score ≤ grade 2, as per a slightly modified version (Arber et al., 2016) of the European Consensus Criteria for Grading Myelofibrosis, (Thiele et al., 2005).
- •Life expectancy > 36 weeks.
- •Able to swallow capsules.
- •Amenable to blood draws, spleen size determination, bone marrow evaluations, and peripheral blood sampling during the study.
- •Must have discontinued prior therapy for condition under study for 2 weeks (4 weeks for interferon) prior to study drug initiation.
- •Agrees to use an approved method of contraception from Screening until 28 days after last administration of the study drug.
- •If male, agrees not to donate sperm or father a child for at least one month after the last dose of the study medication.
排除标准
- •Eastern Cooperative Oncology Group (ECOG) questionnaire score of 3 or greater.
- •Currently pregnant, planning on being pregnant in the following 6 months or currently breastfeeding.
- •Currently residing outside the United States.
- •History of splenectomy.
- •Unresolved treatment related toxicities from prior therapies (unless resolved to ≤ Grade 1).
- •Uncontrolled active infection.
- •Known positive for HIV if not well-controlled (i.e., undetectable viral load), or infectious hepatitis, type A, B or C.
- •Current use of monoamine oxidase A and B inhibitors (MAOIs).
- •Evidence at the time of screening of increased risk of bleeding, including any of the following:
- •Activated partial thromboplastin time (aPTT) > 1.3 x the upper limit of normal
- •International normalized ratio (INR) >1.3 x the local upper limit of normal
- •History of severe thrombocytopenia or platelet dysfunction unrelated to a myeloproliferative disorder or its treatment
- •Known bleeding disorder (e.g., dysfibrinogenaemia, factor IX deficiency, haemophilia, Von Willebrand's disorder, Disseminated Intravascular Coagulation [DIC], fibrinogen deficiency, or other clotting factor deficiency)
- •Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to haemolysis, or leukaemic infiltration) 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 x the local upper limit of normal
- •Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment with the investigational drug.
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IMG-7289 or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates their participation.
- •Patients with impaired decision-making capacity.
研究组 & 干预措施
IMG-7289 in ET and PV Patients
Experimental
Oral daily dose of 0.6 mg/kg/day IMG-7289 will be administered:
- The initial pilot period will enroll 8 participants to receive oral daily dose of IMG-7829 for 24 weeks, iteratively as long as there is clinical benefit in the absence of excess toxicity.
- The second stage group will enroll an additional 16 participants to receive IMG-7829 for over 2 years, iteratively as long as there is clinical benefit in the absence of toxicity.
干预措施: IMG-7289 (Drug)
结局指标
主要结局
Hematologic Response Rates
时间窗: 24 Weeks
As evaluated by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) response criteria.
次要结局
- Incidence of Treatment-Related Toxicity(Up to 3 Years)
- Change in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)(Baseline, Up to 3 Years)
- Change in Mutational Allele Burden(Baseline, Up to 3 Years)
- Change in Spleen Size in Centimeters(Baseline, Up to 3 Years)
- Change in Fibrosis Score(Baseline, Up to 3 Years)
研究者
Terrence J Bradley, MD
Assistant Professor
University of Miami
研究点 (1)
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