BMS CA180157: A Phase I Combination Study of Dasatinib Plus Vorinostat in Accelerated Phase, Chronic Phase Refractory to Second Line Therapy or Blast Crisis Chronic Myelogenous Leukemia (CML), and in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (ALL)

City of Hope Medical Center4 个研究点分布在 1 个国家目标入组 5 人开始时间: 2008年9月1日最近更新: 2012年7月17日

适应症

试验速览

阶段: 1 期
状态: 已完成
发起方
入组人数: 5
试验地点: 4
主要终点: Maximum tolerated dose

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

RATIONALE: Dasatinib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving dasatinib together with vorinostat may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of dasatinib when given together with vorinostat in treating patients with accelerated phase or blastic phase chronic myelogenous leukemia or acute lymphoblastic leukemia.

详细描述

OBJECTIVES:

To define the maximum tolerated dose of dasatinib and vorinostat in patients with accelerated phase or blastic phase chronic myelogenous leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.
To assess the toxicity of this regimen in these patients.
To assess, preliminarily, the efficacy of this regimen in these patients.

Secondary

To perform correlative studies relevant to this regimen.

OUTLINE: This is a multicenter study.

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

•DISEASE CHARACTERISTICS:
•Diagnosis of 1 of the following hematologic malignancies:
•Chronic myelogenous leukemia meeting 1 of the following criteria:
•In accelerated phase, defined by the presence of ≥ 1 of the following:
•At least 15% but < 30% blasts in peripheral blood and/or bone marrow
•At least 30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that < 30% blasts are present in bone marrow)
•At least 20% basophils in peripheral blood
•Platelet count < 100,000/mm³ (unrelated to therapy) OR platelet count > 100,000/mm³ and unresponsive to therapy
•Cytogenetic evidence of clonal evolution
•Increasing spleen size and increasing WBC count and unresponsive to therapy
•In blastic phase (blast crisis), defined by the presence of ≥ 1 of the following:
•At least 30% blasts in peripheral blood and/or bone marrow
•Extramedullary infiltrates of leukemic cells (other than liver or spleen involvement)
•Philadelphia chromosome-positive acute lymphoblastic leukemia meeting any of the following criteria:
•Newly diagnosed or relapsed disease
•Previously treated with chemotherapy, stem cell transplantation, or tyrosine kinase inhibitors (TKIs)
•No active CNS involvement
•PATIENT CHARACTERISTICS:
•ECOG performance status 0-2
•Total bilirubin < 2.0 times upper limit of normal (ULN)
•AST and ALT ≤ 2.5 times ULN
•Serum sodium, potassium, magnesium, phosphate, and calcium ≥ lower limit of normal
•Not pregnant or nursing
•Negative pregnancy test
•Fertile patients must use effective contraception during and for ≥ 4 weeks after discontinuation of study drug
•Able to take oral medication
•No active post-transplantation-related infections (e.g., fungal or viral infection)
•No active acute graft-versus-host disease (GVHD) of any grade
•No chronic GVHD (other than mild skin, oral, or ocular GVHD not requiring systemic immunosuppression)
•No other malignancy that required radiotherapy or systemic treatment within the past 5 years
•No concurrent medical condition that may increase the risk of toxicity, including pleural or pericardial effusion of any grade
•No cardiac conditions, including any of the following:
•Uncontrolled angina, congestive heart failure, or myocardial infarction within the past 6 months
•Diagnosed congenital long QT syndrome
•History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
•Prolonged QTc interval (i.e., QTc > 450 msec) on baseline EKG
•No hypokalemia or hypomagnesemia that cannot be corrected prior to dasatinib administration
•No history of significant bleeding disorder unrelated to cancer, including any of the following:
•Diagnosed congenital bleeding disorder (e.g., von Willebrand's disease)
•Acquired bleeding disorder diagnosed within the past year (e.g., acquired anti-factor VIII antibodies)
•Ongoing or recent (i.e., within the past 3 months) significant gastrointestinal bleeding
•No prisoners or individuals who are compulsorily detained (i.e., involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
•PRIOR CONCURRENT THERAPY:
•See Disease Characteristics
•Recovered from prior therapy
•No prior HDAC inhibitors or compounds with HDAC inhibitor-like activity (e.g., valproic acid) as anti-tumor therapy
•Prior valproic acid for the treatment of seizures allowed provided it was not given within the past 30 days
•Prior allogeneic stem cell transplantation allowed
•More than 4 weeks since prior chemotherapy other than TKI (6 weeks for nitrosoureas and mitomycin)
•More than 2 weeks since prior radiotherapy
另有 11 项未显示

排除标准

未提供

结局指标

主要结局

Maximum tolerated dose

时间窗: 21 days after the beginning of treatment

Toxicity as assessed by NCI CTCAE v3.0

时间窗: 21 days from the beginning of the last course of treatment

Response rate