Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome (MDS) Who Have Been Relapsing After, or Are Refractory to, Hypomethylator Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Number of Participants With Complete Response (CR)
研究概览
简要总结
The goal of this clinical research study is to learn if clofarabine when given in combination with cytarabine can help to control myelodysplastic syndrome (MDS) after the disease could not be controlled with standard therapy. The safety of this treatment will also be studied.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Cytarabine is designed to insert itself into DNA (the genetic material of cells) of cancer cells and stop the DNA from repairing itself.
详细描述
Induction Cycles:
If you are found to be eligible to take part in the study, on Days 1-5 of each cycle , you will receive clofarabine by vein over 1-2 hours.
On Days 1-7 of each cycle, you will receive cytarabine by injection under the skin over several seconds 2 times a day.
You may receive up to 3 cycles at this dose and schedule (also called "induction cycles"). There are 7 treatment days in each cycle but the total length of one cycle (including rest and recovery period) is usually between 4 and 8 weeks.
Consolidation Cycles:
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
- •Age >/= 18 years.
- •Diagnosis of MDS confirmed within 10 weeks prior to study entry according to World Health Organization (WHO) or French-American-British (FAB) criteria. Patients are either not eligible for or choose not to proceed with a stem cell transplant.
- •MDS classified as follows: refractory anemia with excess blasts (RAEB-1) (5%-9% BM blasts); RAEB-2 (10%-19% BM Blasts); chronic myelomonocytic leukemia (CMML) (5%-19% Bone Marrow (BM) blasts); RAEB-t (20%-29% BM blasts) AND/OR by International Prostate Symptom Score (IPSS): intermediate-2 and high risk patients.
- •No response, progression, or relapse (according to 2006 International Working Group (IWG) criteria; see section 8 for details) following at least 4 cycles of either azacitidine or decitabine, or following at least 2 cycles of SGI-110, which were completed within the last 2 years - AND/OR - intolerance to azacitidine, decitabine, or SGI-110 defined as drug-related >/= grade 3 hepatic or renal toxicity leading to treatment discontinuation during the preceding 2 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of </=
- •Willing to adhere to and comply with all prohibitions and restrictions specified in the protocol.
- •Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- •Active infection not adequately responding to appropriate antibiotics (i.e. ongoing temperatures of >/= 38 degree Celsius).
- •Total bilirubin >/= 1.5 mg/dL and not related to hemolysis or Gilbert's disease. Patients with total bilirubin >/= 1.5 mg/dL to 3 mg/dL are eligible if at least 75% of the bilirubin is indirect.
- •Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) >/= 2.5 x the upper limit of normal.
- •Serum creatinine > 1.5 mg/dL.
- •Female patients who are pregnant or lactating.
- •Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices (IUD), double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study.
- •Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
- •Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
- •No prior treatment with cytarabine or clofarabine. Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, Granulocyte-macrophage colony-stimulating factor (GM-CSF), procrit, aranesp, thrombopoietins) is allowed at any time prior to or during study if considered to be in the best interest of the patient.
- •Psychiatric illness or social situation that would limit the patient's ability to comply with study requirements.
研究组 & 干预措施
Clofarabine + Cytarabine
Induction:
Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7)
Consolidation:
Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5)
干预措施: Clofarabine (Drug)
Clofarabine + Cytarabine
Induction:
Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7)
Consolidation:
Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5)
干预措施: Cytarabine (Drug)
结局指标
主要结局
Number of Participants With Complete Response (CR)
时间窗: 4 weeks after first cycle
Complete Response Criteria (CR must last for at least 4 weeks): Marrow: \</= 5% myeloblasts with normal maturation of all cell lines; Persistent dysplasia noted; Blood: Hemoglobin (Hb) \>/= 11 g/dL (untransfused, patient not on EPO); Neutrophils \>/= 1x109/L (not on myeloid growth factor); Platelets \>/= 100 \* 109/L (not on thrombopoietic agent); No blasts. Bone marrow aspirate and/or biopsy at the end of course 1 (day 28 +/- 7 days). The method of Thall, Simon, and Estey used to monitor response.
次要结局
- Overall Survival (OS)(5 years)