NCT01253447已完成2 期
A Phase 2 Study of the AKT Kinase Inhibitor MK-2206 in Patients With Relapsed Refractory Acute Myelogenous Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Number of Participants With a Response of CR, CRp, or PR
研究概览
简要总结
This phase II trial is studying how well AKT inhibitor MK-2206 works in treating patients with relapsed or refractory acute myeloid leukemia (AML). AKT inhibitor MK-2206 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. Determine the proportion of patients achieving Morphologic Complete Response (CR), Morphologic CR with incomplete count recovery (CRp) or Partial Response (PR) as best response within 3 cycles of therapy with MK-2206.
SECONDARY OBJECTIVES:
I. Describe the disease-free survival of patients that achieve CR/CRp.
II. Determine the toxicity profile of single-agent MK-2206 in this patient population.
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
- •Patients must have histologically or cytologically confirmed AML other than acute promyelocytic leukemia (2008 World Health Organization (WHO) classification)
- •Patients must have persistent or relapsing disease requiring 2nd salvage therapy (e.g. treatment for second or higher relapse or for primary refractory disease after failure of two prior treatment regimens); duration of prior complete remission < 12 months if not refractory disease; patients with prior autologous and allogeneic hematopoietic stem cell transplantation are eligible if patients are off immunosuppression for >1 month and have no evidence of active graft versus host disease (GVHD) except grade 1 skin GVHD
- •Patients age >= 60 years with less than two prior treatment regimens not candidates for or have refused standard chemotherapy, excluding subjects with acute promyelocytic leukemia (APL) or with favorable cytogenetic abnormalities [inv16, t(8;21)]
- •Patient at the time of enrollment should not be a candidate for allogeneic stem cell transplantation
- •The Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Serum creatinine or calculated creatinine clearance =< 1.5 * upper limit of normal (ULN) OR >= 60 mL/min for patients with creatinine levels > 1.5 * institutional ULN
- •Serum total bilirubin =< 2 * ULN OR direct bilirubin =< ULN for patients with total bilirubin levels > 2 * ULN, unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis
- •asparate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT /SGPT) =< 2.5 * ULN or =< 5 * ULN unless considered to be secondary to leukemic involvement
- •Fasting serum glucose =< 150 mg/dl
- •HBA1c =< 9%
- •Female patient of childbearing potential must have a negative serum or urine pregnancy test beta- Human chorionic gonadotropin (hCG) within 72 hours prior to receiving the first dose of study medication; the effects of MK-2206 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treatment physician immediately
- •Patient, or the patient"s legal representative, has voluntarily agreed to participate by giving written informed consent
- •Patient is able to swallow tablets and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis
排除标准
- •Patients may not be receiving any other investigational agents
- •Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
- •Active uncontrolled infection
- •Systemic chemotherapy (with the exception of hydroxyurea) within 14 days (or within 5 half-lives for an investigational agent) prior to first dose of study drug, unless there is evidence of rapidly progressive disease; persistent chronic clinically significant toxicities from prior chemotherapy must not be > grade 1
- •Patients with central nervous system (CNS) involvement
- •Patient has known hypersensitivity to the components of study drug or its analogs
- •Uncontrolled congestive heart failure, unstable angina pectoris
- •Uncontrolled cardiac arrhythmia
- •History or current evidence of a myocardial infarction during the last 6 months
- •corrected Q-T interval (QTc) prolongation > 450 msec (Bazett's Formula)
- •Congenitally long QT syndrome, has received any marketed or experimental compound in the last 4 weeks or 5 half lives (whichever is shorter) prior to entering the study with possible or known effects of QT prolongation
- •Patient with symptomatic bradycardia, or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2)
- •Patient with uncontrolled hypertension (i.e., i.e., sustained systolic blood pressure >= 160 or diastolic >= 90); patients who are controlled on antihypertensive medication will be allowed to enter the study
- •Patient with poorly controlled diabetes defined as HBA1C > 9%
- •Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
- •Patient is known to be Human Immunodeficiency Virus (HIV)-positive with history of AIDS defining conditions; or CD4 cells prior to leukemia onset =< 400 cells/mm^3; or patients receiving antiretroviral therapy that affects CYP3A4 such as protease inhibitors, efavirenz, nevirapine, or zidovudine
- •Patient has active Hepatitis B or C or active Hepatitis A
研究组 & 干预措施
Treatment (Akt inhibitor MK2206)
Experimental
Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle
干预措施: Akt inhibitor MK2206 (Drug)
Treatment (Akt inhibitor MK2206)
Experimental
Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Number of Participants With a Response of CR, CRp, or PR
时间窗: 12 weeks of treatment
Responses defined by International Working Group (IWG) 2003 Response Criteria: Morphologic Complete Response (CR): Peripheral blood counts: No circulating blasts, Neutrophil count \>/= 1.0 x10\^9/L, Platelet count \>/= 100 x10\^9/L; Bone marrow aspirate and biopsy: \</= 5% blasts, No detectable Auer rods, No extramedullary leukemia. Partial Response (PR): No circulating blasts, Neutrophil count \>/=1.0 x10\^9/L, Platelet count \>/= 100 x10\^9/L, \>/= 50 % reduction in bone marrow blast to 6% to 25%, or blasts \</= 5% if Auer rods are present. Morphologic CR with incomplete count recovery (CRp): All criteria for CR except for residual neutropenia (\<1x10\^9/L) or thrombocytopenia (\<100 x10\^9/L).
Number of Participants With Treatment-related Non-hematological Toxicity
时间窗: Up to 30 days post-treatment
Toxicity assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 4.0 (CTCAEv4.0)
次要结局
- Maximum Percentage Change in Apoptosis(Baseline to 12 courses)
研究者
研究点 (2)
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