Phase II Study of Idarubicin, Cytarabine, and Vorinostat in Patients With High-Risk MDS and AML
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 106
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS) at 7 Months
研究概览
简要总结
The goal of this clinical research study is to find the highest safe dose of vorinostat that can be given in combination with idarubicin and ara-C for the treatment of AML and high-risk MDS.
Once the highest safe dose is found, researchers will then try to learn if this combination treatment can help to control AML and high-risk MDS in newly diagnosed patients. The safety of this treatment combination will also be studied.
详细描述
The Study Drugs:
Vorinostat is designed to change the gene expression profile of leukemia cells, which may cause the cells to die.
Idarubicin is designed to cause breaks in DNA (the genetic material of cells). This may cause cancer cells to die.
Ara-C is designed to insert itself into DNA of cancer cells and stop the DNA from repairing itself.
This dose combination has not been tested in humans before, at this dose level and schedule.
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
- 15 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of 1) AML (World Health Organization (WHO) classification definition of >/= 20% blasts), or 2) intermediate-2 or high-risk MDS (defined by the IPSS classification2).
- •Patients aged 15 to 65 years;
- •For the initial run-in phase of the study, patients with relapsed or refractory disease or patients with secondary untreated disease are eligible, however, these patients must not have had prior exposure to a histone deacetylase inhibitor, prior antecedent hematological disorder or secondary disease with complex cytogenetics.
- •For the actual phase II portion of the study: patients must be chemonaïve, i.e., not have received any chemotherapy (except hydrea) for AML or MDS. They may have received hypomethylating agents for prior MDS and transfusions, hematopoietic growth factors or vitamins. Temporary prior measures such as apheresis or hydrea are allowed;
- •In those patients that have received prior therapy, at least 2 weeks need to have elapsed before participating in this study. Treatment may start earlier if deemed in the best interest of the patient after discussion with the PI of the study ;
- •Eastern Cooperative Oncology Group (ECOG) performance status </= 2
- •Serum biochemical values with the following limits unless considered due to leukemia: creatinine </=2 mg/dl; total bilirubin </=2 mg/dL, unless increase is due to hemolysis or congenital disorder; transaminases (SGPT or SGOT) </=2.5* upper limit of normal (ULN);
- •Ability to swallow oral medication;
- •Ability to understand and provide signed informed consent;
- •Cardiac ejection fraction must be >/=50% (by either multiple gated acquisition scan (MUGA) scan or echocardiography).
- •Diagnosis of 1) AML (WHO classification definition of > 20% blasts), or 2) intermediate-2 or high-risk MDS (defined by the International Prognostic Scoring System (IPSS) classification) with Flt-3 mutation. Flt-3 extension phase.
- •Patients aged 15 to 65 years are eligible. Flt-3 extension phase.
- •Patients with relapsed or refractory disease or patients with secondary untreated disease are eligible, however, these patients must not have had prior exposure to a histone deacetylase inhibitor. All patients should be Flt-3 positive. Flt-3 extension phase.
- •Patients with newly diagnosed Flt3 positive AML are allowed. Flt-3 extension phase.
- •In those patients that have received prior therapy, at least 2 weeks need to have elapsed before participating in this study. Treatment may start earlier if deemed in the best interest of the patient after discussion with the PI of the study. Flt-3 extension phase.
- •ECOG performance status </=
- •Flt-3 extension phase.
- •Serum biochemical values with the following limits unless considered due to leukemia. creatinine </=2 mg/dl; total bilirubin </=2 mg/dL, unless increase is due to hemolysis or congenital disorder - transaminases (SGPT or SGOT) </=2.5* ULN. Flt-3 extension phase.
- •Ability to swallow oral medication. Flt-3 extension phase.
- •Ability to understand and provide signed informed consent. Flt-3 extension phase.
- •Cardiac ejection fraction must be >/=50% (by either MUGA scan or echocardiography). Flt-3 extension phase.
排除标准
- •Diagnosis of acute promyelocytic leukemia;
- •Active, uncontrolled, systemic infection considered opportunistic, life threatening or clinical significant at the time of treatment, or any severe concurrent disease, which in the opinion of the investigator and after discussion with the principal investigator, would make the patient inappropriate for study entry;
- •Male and female patients who are fertile agree to use an effective barrier method of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 7 days of study enrollment (applies only if patient of childbearing potential. Non childbearing is defined as 1 year or more postmenopausal or surgically sterilized);
- •Symptomatic central nervous system (CNS) involvement;
- •Patient is unable to take and/or tolerate oral medications on a continuous basis;
- •Patient has known human immunodeficiency virus (HIV) infection or known HIV-related malignancy;
- •Patient has active hepatitis B or C infection. Active disease is defined as elevated liver enzymes and/or clinical symptoms of hepatitis in addition to positive blood test for hepatitis surface antigen. In the absence of elevated liver enzymes and/or clinical symptoms, the blood test for hepatitis core antigens is not required.
- •Patient is pregnant or breast-feeding;
- •Patient has a known allergy or hypersensitivity to any component of vorinostat;
- •Patient has a history of thrombotic disorders;
- •History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent.
- •Diagnosis of acute promyelocytic leukemia. Flt-3 extension phase.
- •Active, uncontrolled, systemic infection considered opportunistic, life threatening or clinical significant at the time of treatment, or any severe concurrent disease, which in the opinion of the investigator and after discussion with the principal investigator, would make the patient inappropriate for study entry. Flt-3 extension phase.
- •Male and female patients who are fertile agree to use an effective barrier method of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 7 days of study enrollment (applies only if patient of childbearing potential. Non childbearing is defined as 1 year or more postmenopausal or surgically sterilized). Flt-3 extension phase.
- •Symptomatic CNS involvement. Flt-3 extension phase.
- •Patient is unable to take and/or tolerate oral medications on a continuous basis. Flt-3 extension phase.
- •Patient has known human immunodeficiency virus (HIV) infection or known HIV-related malignancy. Flt-3 extension phase.
- •Patient has active hepatitis B or C infection. Active disease is defined as elevated liver enzymes and/or clinical symptoms of hepatitis in addition to positive blood test for hepatitis surface antigen. In the absence of elevated liver enzymes and/or clinical symptoms, the blood test for hepatitis core antigens is not required. Flt-3 extension phase.
- •Patient is pregnant or breast-feeding. Flt-3 extension phase.
- •Patient has a known allergy or hypersensitivity to any component of vorinostat. Flt-3 extension phase.
- •Patient has a history of thrombotic disorders. Flt-3 extension phase.
- •History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent. Flt-3 extension phase.
研究组 & 干预措施
Idarubicin + Ara-C + Vorinostat
Idarubicin 12 mg/m^2 by vein (IV) over 1 hour daily for 3 days (days 4 to 6). Ara-C (Cytarabine) 1.5 g/m^2 IV as a continuous infusion over 24 hours daily (days 4 to 7). Vorinostat initial dose level 500 mg orally three times a day for 3 days (days 1 to 3).
干预措施: Idarubicin (Drug)
Idarubicin + Ara-C + Vorinostat
Idarubicin 12 mg/m^2 by vein (IV) over 1 hour daily for 3 days (days 4 to 6). Ara-C (Cytarabine) 1.5 g/m^2 IV as a continuous infusion over 24 hours daily (days 4 to 7). Vorinostat initial dose level 500 mg orally three times a day for 3 days (days 1 to 3).
干预措施: Cytarabine (Drug)
Idarubicin + Ara-C + Vorinostat
Idarubicin 12 mg/m^2 by vein (IV) over 1 hour daily for 3 days (days 4 to 6). Ara-C (Cytarabine) 1.5 g/m^2 IV as a continuous infusion over 24 hours daily (days 4 to 7). Vorinostat initial dose level 500 mg orally three times a day for 3 days (days 1 to 3).
干预措施: Vorinostat (Drug)
结局指标
主要结局
Progression Free Survival (PFS) at 7 Months
时间窗: PFS Evaluation at 7 months
Progression-free survival defined as time from date of randomization to first occurrence of having documented disease progression or death due to any cause, whichever comes first. Progression based on tumor assessments according to Response Evaluation Criteria in Solid Tumors (RECIST). Participants were followed from baseline to disease progression with PFS evaluation at 7 months.
次要结局
- Participant Response(Monitoring with each 4 week cycle, up to 18 cycles of treatment)