A Phase 2 Trial of Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS) Who Are Ineligible for Other Leukemia Protocols
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Survival at Day 60
研究概览
简要总结
The goal of this clinical research study is to learn if the combination of azacitidine and vorinostat can help to control AML or MDS better than azacitidine alone. The safety of this drug combination will also be studied.
详细描述
The Study Drugs:
Azacitidine is designed to block certain genes in cancer cells whose job is to stop the function of the tumor-fighting genes. By blocking the "bad" genes, the tumor-fighting genes may be able to work better.
Vorinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 with newly diagnosed AML or MDS (Intermediate 1 or higher risk)
- •Patient must have at least one of the following: a. Creatinine >/= 2 mg/dL; b. total Bilirubin >/= 2 mg/dL; c.ECOG Performance Status equal to 3 or 4; and d. is ineligible for participation on a protocol of higher priority
- •Patients must provide written informed consent.
- •Patients must be age > 18 years due to lack of safety information with these agents in children.
- •Patient agrees to: 1) Use 2 adequate methods of contraception to prevent pregnancy (either 2 barrier methods or a barrier method plus a hormonal contraceptive method) or 2) abstain from heterosexual activity throughout the study starting with Visit
- •Female patients of childbearing potential should have a negative pregnancy test (serum) within 72 hrs. of study enrollment.
排除标准
- •Patients must not have the favorable cytogenetic abnormalities of inv (16), t (16;16), t (8;21), or t (15;17).
- •Patients receiving any anti-leukemic therapy with the exception of Hydroxyurea prior to study enrollment. Prior growth factor therapy is acceptable. Hydroxyurea could be used at the discretion of the treating physician. A single or a two day dose of cytarabine (up to 3 g/m^2) for emergency use is allowed as prior therapy.
- •Patient has a prior history of treatment with HDAC inhibitors. Patients who have received valproic acid (VPA) for the treatment of seizures may be enrolled on this study, but must not have received VPA within 30 days of study enrollment.
- •Patient is unable to take and/or tolerate oral medications on a continuous basis, examples include patients on a ventilator, or have altered mental status that precludes safe oral route of administration.
- •Patient has active hepatitis A, B, or C infection.
- •Patient is pregnant or breast-feeding.
- •Patient has a known allergy or hypersensitivity to any component of vorinostat or azacitidine.
- •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.
研究组 & 干预措施
Vorinostat with Azacitidine
ARM A: Azacitidine 75 mg/m^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
干预措施: Vorinostat (Drug)
Vorinostat with Azacitidine
ARM A: Azacitidine 75 mg/m^2/day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Vorinostat 200 mg by mouth three time a day with food for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
干预措施: Azacitidine (Drug)
Azacitidine
ARM B: Azacitidine 75 mg/m^2 /day by vein over 15 - 30 minutes daily for 5 days (Days 1 - 5). Courses repeated every 3 to 8 weeks.
干预措施: Azacitidine (Drug)
结局指标
主要结局
Survival at Day 60
时间窗: Phase II, Baseline to 60 days following first treatment.
Assessment of survival for outcome done on 60 days following therapy and includes participants alive for at least 60 days. Survival is calculated from start of therapy until death from any cause.
Response Rate
时间窗: 12-18 Months
Number of participants with Complete Response (CR) in AML requiring disappearance of all signs and symptoms related to disease, normalization of peripheral counts (absolute neutrophil count 10\^9/L or more, platelet count 100 x 10\^9/L or more), and a marrow with 5% or less marrow blasts; a hematologic improvement (HI) defined as a CR except for a platelet count increase by 50% to above 30 x 10\^9/L. For MDS, the International Working Group criteria used to assess response.
次要结局
未报告次要终点