NCT01032148终止1 期
Phase I Study of LBH589, A Novel Oral Deacetylase Inhibitor in Patients With Recurrent or Refractory Hodgkin or Non-Hodgkin's Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Determine maximum tolerated dose (MTD) of LBH589
研究概览
简要总结
The purpose of this study is to find out the effects of a drug called LBH589 when given to people with recurrent or refractory Hodgkin or Non-Hodgkin's lymphoma. The safety of this drug will also be studied. The participants' physical state, changes in the size of the tumor, or state of Hodgkin or non-Hodgkin's Lymphoma, and laboratory findings taken while on-study will help the researchers decide if LBH589 is safe and effective.
详细描述
This is an open-label, standard 3-3 dose finding scheme with a modification that allows intra-patient dose modification to determine maximum tolerated dose and toxicity profile of LBH589 in patients with recurrent or refractory Hodgkin's or non-Hodgkin's lymphoma.
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
- •Male or female patients age ≥ 18 years old with relapsed/refractory Hodgkin lymphoma or NHL patients who have relapsed or are refractory after receiving a minimum of two prior therapies
- •Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- •Laboratory requirements:
- •ANC ≥ 1.5 x 10(9th)/L, unless due to bone marrow involvement with lymphoma
- •Hemoglobin ≥ 9 g/dl without packed red blood cell dependency, unless due to bone marrow involvement with lymphoma
- •Platelets ≥ 100 x 10(9th)/L, unless due to bone marrow involvement with lymphoma
- •Serum creatinine ≤ 1.5 x Upper limit of Normal, or calculated Creatinine Clearance ≥ 50 mL/min
- •AST and ALT ≤ 2.5 x Upper limit of Normal, unless due to liver involvement with lymphoma
- •Serum bilirubin ≤ 1.5 x Upper limit of Normal
- •Albumin > 3.0 g/dl
- •Serum potassium ≥ Lower limit of Normal
- •Total serum calcium [corrected for serum albumin] or ionized calcium ≥ Lower limits of normal
- •Serum magnesium ≥ Lower limit of Normal
- •Serum phosphorus ≥ Lower limit of Normal
- •TSH ≥ LLN and free T4 within normal limits. Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
- •Baseline MUGA or ECHO must demonstrate LVEF ≥ 50%
- •ECOG Performance Status of ≤ 2
排除标准
- •Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
- •Patients who will need valproic acid for any medication during the study or within 5 days prior to first LBH589 treatment
- •Peripheral neuropathy ≥ CTCAE grade 1
- •Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
- •Patients with congenital QT syndrome
- •History or presence of sustained ventricular tachyarrhythmia.
- •Any history of ventricular fibrillation or torsade de pointes
- •Bradycardia defined as Heart Rate < 50 bpm. Patients with pacemakers are eligible if Heart Rate ≥ 50 bpm
- •Screening EKG with a QTc.450msec
- •Right Bundle branch block + left anterior hemiblock (bifascicular block)
- •Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
- •other clinically significant heart disease (e.g. CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension or history of poor compliance with an antihypertensive regimen)
- •Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
- •Patients with Diarrhea > CTCAE grade 1
- •Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values that could cause unaccepted safety risks or compromise compliance with the protocol
- •Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
- •Concomitant use of CYP3A4 inhibitors
- •Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites(which ever is longer) and who have not recovered from side effects of those therapies
- •Patients who have received either immunotherapy within ≤ 8 weeks;chemotherapy within ≤ 4 weeks or radiation therapy to >30% of marrow-bearing bone within ≤ weeks prior to starting study treatment or who have not yet recovered from side effects of such therapies
- •Patients with an active bleeding tendency or is receiving any treatment with therapeutic doses of sodium warfarin or coumadin derivatives. Low doses of Coumadin (e.g.≤2 mg/day) to maintain line patency is allowed.
- •Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- •Women who are pregnant or breast feeding or women of childbearing potential not using effective method of birth control
- •Male patients whose sexual partners are women of childbearing potential not using effective birth control
- •Patients with prior malignancy within 5 years (except for basal or squamous cell carcinoma, in situ cancer of the cervix or early stage prostate or bladder carcinomas)
- •Patients with known positivity for HIV or hepatitis C: baseline testing for HIV and Hepatitis C is not required
- •Prior allogenic stem cell transplant
- •Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff
- •Patients taking CYP2D6 inhibitors should be carefully monitored, but these drugs are not necessarily contraindicated when use concomitantly with LBH. Use of these drugs is not an exclusion criterion
研究组 & 干预措施
LBH589
Experimental
LBH589 administered orally as once daily dose of 20 mg po q M, W, F on a q 28 day cycle, escalating to a maximum dase of 60 mg
干预措施: LBH589 (Drug)
结局指标
主要结局
Determine maximum tolerated dose (MTD) of LBH589
时间窗: 2 years
次要结局
- Determine toxicity profile in study population(28 days after Cycle 2 Day 1)
- Determine anti-lymphoma activity of LBH589 in (non-CTCL) Hodgkin's and non-Hodgkin's lymphoma patients(2 Years)
研究者
研究点 (1)
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