An Early-Phase Clinical Trial Evaluating ABC294640 in Patients With Refractory/Relapsed Diffuse Large B-cell Lymphoma or Kaposi Sarcoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Evaluate safety of ABC294640 in patients with refractory/relapsed DLBCL or KS
研究概览
简要总结
This is a sequential Phase I and IIa study to identify the maximum tolerated dose and to evaluate safety, tolerability, toxicity, pharmacokinetics and pharmacodynamics of the oral sphingosine kinase inhibitor ABC294640 specifically in patients with diffuse large B-cell lymphoma (DLBCL), including virus-associated (e.g., KSHV- or EBV-associated) DLBCL or Kaposi Sarcoma (KS) after failure of or intolerance to initial standard therapy.
详细描述
Sphingosine Kinase (SK) is an innovative target for anti-cancer therapy due to its critical role in lipid metabolism which drives cancer cell growth. We have found that the SK inhibitor ABC294640 (which is formulated for clinical use as an oral agent) significantly inhibits and reverses progression of virus-associated DLBCL in pre-clinical animal models [Qin et a., 2014]. In addition, we have found that ABC294640 selectively induces death for virus-infected endothelial cells in a laboratory model relevant to KS, with selective sparing of uninfected cells [Dai et al., 2014; Dai et al., 2015]. Both DLBCL and KS disproportionately impact patients with immune-deficiencies, including HIV infection, for whom standard chemotherapeutic approaches are less effective and incur greater side effects. Therefore, this trial which utilizes a well-tolerated, oral agent to inhibit SK for DLBCL and KS patients may provide a unique approach to treatment.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ABC294640
Patients will receive ABC294640 orally in gelatin capsules BID.
干预措施: ABC294640 (Drug)
结局指标
主要结局
Evaluate safety of ABC294640 in patients with refractory/relapsed DLBCL or KS
时间窗: If present, expected within 8 weeks
Determine Maximum tolerated dose (MTD) of ABC294640 in patients with refractory/relapsed DLBCL or KS and determine tolerability at MTD.
时间窗: Patients will be followed until a dose limiting toxicity (DLT) is experienced, if present, expected within the first 8 weeks
次要结局
- Measure plasma levels of ABC294640 (pharmacokinetics) in patients with DLBCL or KS(Days 1 and 28, 1,2, 4, 8 and 24 hours post drug administration)
- Evaluate antitumor activity of ABC294640 in virus-associated DLBCL or KS patients by objective radiographic assessment using PET (DLBCL) or CT (KS) criteria, or measurement of clinically evident skin lesions (KS)(Within 14 Days of Treatment Day 1 and then on Day 28 of Cycles 2, 4, 6, 8, etc., stopping if tumor progression is observed)
- Measure plasma levels of sphingosine-1-phosphate in response to ABC294640 in patients with DLBCL or KS(Days 1,8,15 and 28 in Cycle 1, Days 14 and 28 for all subsequent cycles and at the end of treatment study)
- Measure levels of circulating CD4+ T cell count, KSHV/EBV viral loads, and HIV viral load (if applicable) in response to ABC294640 in patients with DLBCL or KS(Days 1, 8, 15 and 22 for cycles 1-3 and Days 1, 8, 15, 22 and 28 for Cycle 4)