NCT02089230终止1 期
Phase I/II Trial of MEK Inhibitor MEK162 in Patients With Relapsed and or Refractory Acute Myeloid Leukemia and Patients With Poor Prognosis Acute Myeloid Leukemia Not Suitable for or Unwilling to Receive Standard Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of MEK 162 in Participants With Advanced Leukemias
研究概览
简要总结
The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of MEK162 that can be given to patients with advanced leukemia.
This is an investigational study. MEK162 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.
Up to 57 patients total will take part in both phases of this study . All will be enrolled at MD Anderson.
The goal of Phase 2 of this clinical research study is to learn if MEK162 can help to control AML in older patients with advanced leukemia. The safety of this drug will also be studied.
This is an investigational study. MEK162 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work.
Up to 57 patients total will take part in both phases of this study. All will be enrolled at MD Anderson.
详细描述
Phase I:
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 2 groups of 3-6 participants will be enrolled in Phase 1 of the study.
If you are enrolled in Phase 1, the dose of MEK162 you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of MEK162. The second group will receive a higher dose of MEK162 than the group before it, if no intolerable side effects were seen. This is designed to find the highest tolerable dose of MEK 162.
Participants in Phase 2 will then receive the highest tolerated dose that was found in Phase 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •PHASE I -- a. Primary or secondary AML according to World Health Organization (WHO) classification, with relapsed or refractory disease or newly diagnosed older subjects (greater than or equal to 65 years of age), not candidates for intensive chemotherapy; b. Subjects with MDS, International Prognostic Scoring System (IPSS) Int-2 or high risk (RAEB-2 only, i.e. greater than or equal to 10% blast) who are resistant or intolerant to standard treatment and are not candidates for transplantation; c. Subjects with ALL, relapsed, refractory or intolerant to standard treatment and for whom no effective treatment options are available.
- •Age greater or equal to 18 years.
- •Patients should be willing and able to give informed consent.
- •Eastern Cooperative Group (ECOG) PS less than or equal to
- •PHASE II -- Patients aged 60 and older with newly diagnosed primary or secondary AML according to WHO classification, without any prior therapy for AML with the exception of (a) emergency Leukapheresis and (b) emergency treatment for hyperleukocytosis with hydroxyurea that is allowed until 24 hours before start of the trial treatment. Note: Prior therapy for preexisting hematological condition e.g. MDS or Myeloproliferative Disorder (MPD), including but not limited to hypomethylating agents is allowed until at least 2 weeks have elapsed from completion of that agent before the first dose of MEK
- •Patients must meet at least one of the following conditions: a. Age greater than or equal to 75 years; b. Age greater or equal to 60 and less than 75 years with at least one of the following poor prognostic factors: i. Secondary AML, as determined by known and documented exposure to chemotherapy or radiation therapy; ii. antecedent history of MDS or myeloproliferative disorder according to WHO criteria for at least 3 months prior to trial entry; iii. unfavorable cytogenetic abnormalities including chromosome 5 and 7 as well as complex; iv. ECOG Performance status
- •(Phase II ONLY)
- •Patients are willing and able to give informed consent. (Phase II only)
- •Only patients with mutated RAS (KRAS and NRAS) mutations are eligible to participate. (Phase II only)
- •Adequate cardiac function defined as: --left ventricular ejection fraction (LVEF) greater than or equal to 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram; -- QTcF interval less than or equal to 480 ms. (Phase II only)
排除标准
- •PHASE I and II -- Administration of any antineoplastic therapy within at least 4 weeks (cytotoxic chemotherapy) or 2 weeks (biological and targeted therapy; hypomethylating agents are considered to be biological therapy) of that therapy of the first MEK 162/MEK 162 dose; except the use of hydroxyurea which can be administered up to 5 g/day up to 24 hours before the initiation of the study drug.
- •Patients should not have received an investigational agent for at least 2 weeks prior to the first study drug dose.
- •Clinical evidence of active Central Nervous System (CNS) leukemia requiring active therapy; prior CNS leukemia well-controlled by ongoing therapy is allowed.
- •Active and uncontrolled infection including but not limited to known infection with HIV, active hepatitis B, or hepatitis C.
- •Major surgery within two weeks prior to trial entry.
- •Liver function tests above the following limits at the screening: total bilirubin > 1.5 x Upper Limit of Normal (ULN) unless related to Gilbert's syndrome or hemolysis, AST and/or ALT > 2.5 X ULN, or for subjects with liver involvement Aspartate Aminotransferase (AST) and/or Alanine transaminase (ALT) > 5 x ULN.
- •Serum creatinine > 1.5 x ULN and/or Creatinine Clearance (CrCl) < 30 mL/min at screening (calculation according to Cockcroft & Gault formula).
- •Pregnant or nursing (lactating) women;
- •Female patients of childbearing potential and male patients with partners of childbearing potential who are not willing ot use highly effective methods of contraception throughout the study and for 1 month after study drug discontinuation. Highly effective contraception methods include: **Total abstinence; or **Male or female sterilization; **Combination of any two of the following (a+b or a+c or b+c); a. Use of oral, injected, or implanted hormonal methods of contraception; b. Placement of an intrauterine device (IUD) or intrauterine system (IUS); c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
- •Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at screening;
- •History of significant difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions that may hamper compliance and/or absorption of the tested product.
- •Has significant cardiac conduction abnormalities and/ or pacemaker or any of the following criteria: -- History of acute coronary syndromes (including myocardial infarction, unstable angina, Coronary Artery Bypass Grafting (CABG), coronary angioplasty, or stenting) <6 months prior to screening, --Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening --Uncontrolled arterial hypertension, defined as BP > 140/100 mmHg (average of 3 consecutive readings)
- •History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO).
- •Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes).
- •Subjects with active other tumors, except early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN).
- •Patients who have neuromuscular disorders that are associated with elevated Creatinine Kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
- •Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment. NB: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment.
- •Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
研究组 & 干预措施
Phase I Cohort 1 - MEK 162
Experimental
Phase I Starting Dose of MEK 162: 30 mg by mouth twice a day in a 28 day cycle.
干预措施: MEK 162 (Drug)
Phase I Cohort 2 - MEK 162
Experimental
Phase I Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.
干预措施: MEK 162 (Drug)
Phase II Cohort 3 - MDK 162
Experimental
Phase II Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.
干预措施: MEK 162 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of MEK 162 in Participants With Advanced Leukemias
时间窗: 28 days
Maximum tolerated dose is the highest dose level in which \<2 patients of 6 develop dose limiting toxicity (DLT).
次要结局
- Number of Participants With a Response(Assessed after one 28-day cycle of treatment)
研究者
研究点 (1)
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