A Phase II Study of Dasatinib in Chronic Lymphocytic Leukemia in Patients Who Exhibit in Vitro Dasatinib Sensitivity
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- The Number of Participants With In Vitro Dasatinib Sensitivity in Predicting Clinical Activity
研究概览
简要总结
This phase II trial studies how well dasatinib works in treating patients with chronic lymphocytic leukemia (CLL). Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the biologic target activity of dasatinib in CLL patients found to have pre-treatment in vitro dasatinib cytotoxicity (as defined by a >= 50% decrease in absolute lymphocyte count and/or bone marrow CLL count and/or lymph node or spleen size).
SECONDARY OBJECTIVES:
I. To evaluate overall objective response rates per CLL National Cancer Institute (NCI) working group.
II. To determine drug safety and tolerability of dasatinib in patients with CLL.
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
- •Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal information
- •Eastern Cooperative Oncology Group (ECOG) =< 2
- •In vitro dasatinib sensitivity (IC 50 =< 50 nm per MTS assay)
- •Diagnosis of CLL and must meet one of the following:
- •Relapsed CLL in all patients who have failed at least one prior treatment, regardless of risk group
- •OR De novo (treatment-naïve) patients age >= 65 who are not candidates for or do not want to pursue aggressive chemotherapy treatment
- •Have indications for treatment or evidence of progressive disease defined as follows (1996 NCI working group):
- •Massive or progressive splenomegaly
- •Massive lymph nodes (>= 10 cm), nodal clusters (>= 10 cm), or progressive lymphadenopathy
- •Symptomatic anemia and/or thrombocytopenia (Rai stages III or IV disease)
- •Autoimmune hemolytic anemia and/or thrombocytopenia that are poorly responsive to corticosteroid therapy
- •Progressive lymphocytosis with increase in lymphocyte count of >= 50% over a 2-month period or an anticipated doubling time of < 6 months
- •Repeated episodes of infection
- •Have not received CLL treatment within the past 2 weeks
- •Total bilirubin < 2.0 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) =< 2.5 x ULN
- •Alanine aminotransferase (ALT) =< 2.5 x ULN
- •Serum creatinine < 2.0 x ULN
- •International normalized ratio (INR) =< 1.2
- •Platelet (Plt) count > 30,000
- •Ability to take oral medication (dasatinib must be swallowed whole)
- •No clinically significant infections as determined by the investigator
- •Normal corrected QT (QTc) interval (< 450 msec)
- •Serum potassium and magnesium are within normal limits
- •Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (sensitivity =< 25 IU HCG/L) within 72 hours prior to the start of study drug administration
- •Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped prior to study enrollment; women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy
- •After consent, discontinuation ("washout period") of any medications known to contribute significantly to the risk of QT prolongation or interfere with cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) mediated drug metabolism
- •Patient agrees to discontinue St. John's Wort while receiving dasatinib therapy (discontinue St. John's Wort at least 5 days before starting dasatinib)
- •Patient agrees that IV bisphosphonates will be withheld for the first eight weeks of dasatinib therapy due to risk of hypocalcemia
- •Patient agrees to discontinue anti-coagulants and anti-platelet drugs; note: a low dose aspirin regimen (81mg QD) is permitted with close monitoring of the subject's platelets for a level >= 50,000/mm^3
排除标准
- •Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy
- •Pleural or pericardial effusion of any grade
- •Uncontrolled angina, > New York Heart Association (NYHA) class III congestive heart failure or myocardial infarction (MI) within 6 months prior to study enrollment
- •Diagnosed congenital long QT syndrome
- •Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- •Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec)
- •Subjects who are detained or imprisoned are not eligible
- •History of significant bleeding disorder unrelated to cancer, including:
- •Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
- •Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
- •May not take concomitant medications that are generally accepted to have a risk of causing Torsades de Pointes including: (patients must discontinue drug 7 days prior to starting dasatinib)
- •Quinidine, procainamide, disopyramide
- •Amiodarone, sotalol, ibutilide, dofetilide
- •Erythromycin, clarithromycin
- •Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
- •Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, sparfloxacin, lidoflazine
- •Patients already taking other CYP inducers or inhibitors other than those listed above are eligible for the study only after principal investigator (PI) review; dose adjustments and/or monitoring of drug levels where applicable will be made as needed by the PI after consultation with pharmacy
- •Women who:
- •Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or
- •Have a positive pregnancy test at baseline, or
- •Are pregnant or breastfeeding
研究组 & 干预措施
Treatment (dasatinib)
Patients receive dasatinib PO QD during course 1 and if tolerated, BID in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Dasatinib (Drug)
Treatment (dasatinib)
Patients receive dasatinib PO QD during course 1 and if tolerated, BID in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (dasatinib)
Patients receive dasatinib PO QD during course 1 and if tolerated, BID in subsequent courses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
The Number of Participants With In Vitro Dasatinib Sensitivity in Predicting Clinical Activity
时间窗: 8 weeks
Defined by a decrease in absolute lymphocyte count, as determined by peripheral blood complete blood count (CBC) with differential or by bone marrow examination of 50 % and/or a decrease of detectable total lymph node size or spleen size by 50% (either by clinical examination contrast enhanced computed tomography \[CT\]).
次要结局
- Overall Survival(Up to 2 years)
- Incidence of Adverse Events (Number of Participants Affected)(Up to 4 years)
- Objective Response(Up to 2 years)
- Progression-free Survival(Up to 2 years)
研究者
Stephen Spurgeon
Associate Professor
OHSU Knight Cancer Institute