A Pilot Phase II Study of Decitabine, Arsenic Trioxide and Ascorbic Acid for Patients With Myelodysplastic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Patients With an Overall Response of Complete Response (CR) or Partial Response (PR)
研究概览
简要总结
This will be an open-label, non-randomized trial pilot phase II trial open to patients with myelodysplastic syndrome. The purpose of the study is to find out if the combination of decitabine, arsenic trioxide and ascorbic acid is safe.
详细描述
Conventional therapy for MDS has been poor at best. Supportive care with transfusion therapy and antibiotics have remained an option for all patients with myelodysplastic syndrome (MDS).
The only known curative therapy is an allogeneic bone marrow transplant. However due to its high morbidity in this elderly population and the lack of available donors, it is estimated that less than 5% of patients with MDS are candidates for this type of aggressive therapy. Investigational therapies are thus warranted in MDS.
Decitabine shows significant clinical activity in patients with MDS, with moderate toxicity. The major toxicity is myelosuppression with subsequent infection occurring in 20-25% of patients.
Arsenic trioxide is an FDA approved drug for the treatment of patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy. Two pivotal studies of arsenic trioxide in the setting of relapsed APL showed a complete remission rate of 87% with a 36 month survival estimate of 50%. As of May 2004, over 800 patients had received arsenic trioxide in clinical studies or through a compassionate use program, and an additional 3600 patients had received the drug in clinical practice.
Arsenic trioxide shows clinical activity in MDS. Side effects have been noted and are manageable.
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
- •Established diagnosis of MDS (de novo or secondary) fitting either the French American British Cooperative Group (FAB) or World Health Organization (WHO) classification systems as determined by a complete blood count (CBC) and bone marrow biopsy. Patients with >20% bone marrow blasts but <30% bone marrow blasts who would be classified as refractory anemia with excess blasts (RAEB-t) in the FAB and acute myeloid leukemia (AML) in the WHO systems are still eligible for this study. Patients with low risk MDS (IPSS scores low or intermediate -1 (INT-1) must be transfusion dependent to be eligible. Transfusion dependent will be defined as having 2 or more transfusion events within a 90 day period.
- •Eastern Oncology Cooperative Group (ECOG) or WHO performance status of 0-2 (Appendix)
- •Able to provide written informed consent.
排除标准
- •Pregnant females
- •AML defined as > 30% bone marrow blasts.
- •Any malignant disease within the past 2 years, except cervical carcinoma, basal cell carcinoma of the skin, and squamous cell carcinoma of the skin..
- •Off all prior treatment for MDS for at least 4 weeks from entry.
- •Off any investigational agents for at least 4 weeks from entry.
- •Uncontrolled cardiac disease or congestive heart failure as defined by New York Heart Association criteria of Class III or greater.
- •Uncontrolled pulmonary disease.
- •Uncontrolled or active viral or bacterial infection. All infections must have been fully treated with antibiotics.
- •Lab values as specified in the protocol
研究组 & 干预措施
1
Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS
干预措施: Decitabine, Arsenic Trioxide and Ascorbic Acid (Drug)
结局指标
主要结局
Number of Patients With an Overall Response of Complete Response (CR) or Partial Response (PR)
时间窗: after 4 cycles of therapy
Complete response and Partial response are defined using 2000 international working group (IWG) criteria. The Primary criteria for a CR is a repeat bone marrow showing \< 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia . A PR meets all the CR criteria except Blasts decreased by \>50% over pretreatment, or a less advanced myelodysplastic syndrome (MDS) French American British (FAB) classification than pretreatment.
次要结局
- Duration of a Complete or Partial Response Based on Number of People Who Responded.(Up to 5 years or until death)
- Number of Patients With an Unacceptable Toxicity(During the treatment period and for 30 days after last dose of study drug)