A Phase II Trial of LBH589 in Refractory Myelodysplastic Syndromes (MDS) Patients
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 7
- 主要终点
- Overall Response Rate (CR, Marrow CR + PR) of LBH in Patients With Relapsed or Refractory MDS.
研究概览
简要总结
This will be a single arm Phase II study.
详细描述
LBH589 (20 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically or cytological documented diagnosis of myelodysplastic syndrome (MDS).
- •Male or female patients aged >= 18 years old.
- •MDS patients who have failed hypomethylating (azacitidine or decitabine) therapy.
- •Patients with 5q-cytogenic abnormalities must also have progressed on or been intolerant to lenalidomide.
- •Patients with up to and including 30% blasts (FAB RAEB-T) will be eligible to enroll.
- •CMML with >= 5% blasts will be eligible to enroll.
- •ECOG PS 0, 1 or
- •Laboratory values must be as follows:
- •Bilirubin <= 1.5 mg/dL AST/SGOT <= 2.5 x ULN ALT/SGPT Creatinine <= 2.0 mg/dL or 24-hour Creatinine Clearance >= 50 ml/min Albumin >= 3 g/dL Potassium >= lower limit normal (LLN) Phosphorous >= LLN Calcium >= LLN Magnesium >= LLN
- •Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment.
- •Life expectancy >= 12 weeks.
排除标准
- •Prior treatment with an HDAC inhibitor.
- •Prior intensive chemotherapy or high dose ara-C (>= 1 gm/m2)
- •More than one prior single agent chemotherapy regimen. Prior hydroxyurea for cytoreduction will be permitted however.
- •Impaired cardiac function
- •Active CNS disease, including leptomeningeal metastases.
- •Unresolved diarrhea > CTCAE grade
- •Chemotherapy, investigational drug therapy, major surgery < 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.
- •Patient is < 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- •Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method.
- •Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.
- •Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
- •Other concurrent severe, uncontrolled systemic fungal, bacterial, viral or other infection or intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients with uncontrolled coagulopathy.
- •Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.
研究组 & 干预措施
Panobinostat 20 mg
Treatment with LBH589 (Panobinostat) 20 mg
干预措施: Panobinostat (Drug)
Panobinostat 30 mg
Treatment with LBH589 (Panobinostat) 30 mg
干预措施: Panobinostat (Drug)
结局指标
主要结局
Overall Response Rate (CR, Marrow CR + PR) of LBH in Patients With Relapsed or Refractory MDS.
时间窗: Every 8 weeks up to 24 months on-study.
Overall response rate (ORR) is defined by the modified International Working Group (IWG) Response Criteria for MDS. In the marrow, Complete Response (CR) is \<= 5% blasts present with normal maturation of all cell lines. In peripheral blood, CR is defined as hemoglobin \>= 11 g/dL, ANC \>= 1000/mL, and platelets \>= 100,000 with 0% blasts present. Partial Response (PR) is defined the same as CR with blasts decreased by \>= 50% and \>= 5% blasts in the marrow.
次要结局
- Hematologic Improvement, Including Transfusion Independence(Every 8 weeks up to 24 months on-study)
- Time to Disease Progression(Every 8 weeks up to 24 months on-study, every 3 months in follow-up until progression of disease)
- Duration of Response(Every 8 weeks up to 24 months on-study)
- Median Time to Treatment Failure(24 months)
- Median Overall Survival(24 months on-study, patients followed every 3 months in follow-up)
- Safety and Tolerability of LBH589 in Patients With Relapsed/Refractory MDS by Measuring the Number of Participants With Adverse Events(24 months)