NCT01949883已完成1 期
A Phase 1 Study of CPI-0610, a Small Molecule Inhibitor of BET (Bromodomain and Extra-terminal) Proteins, in Patients With Progressive Lymphoma
Constellation Pharmaceuticals0 个研究点目标入组 64 人开始时间: 2013年9月5日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 主要终点
- Frequency of dose-limiting toxicities (DLTs) associated with CPI-0610 administration during the first cycle (first 21 days) of treatment
研究概览
简要总结
First in human, open-label, sequential dose escalation and expansion study of CPI-0610 in patients with progressive lymphoma. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.
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
- •Adults (aged ≥ 18 years)
- •Histologically confirmed diagnosis of a non-Hodgkin or Hodgkin lymphoma that has progressed in spite of prior treatment, and for which additional effective standard therapy is not available
- •Patients may have either measurable or non-measurable disease, but in all cases eligible patients must have disease that can be clinically evaluated for improvement or progression
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- •Adequate hematological, renal, hepatic, and coagulation laboratory assessments
- •Written informed consent to participate in this study before the performance of any study-related procedure
排除标准
- •A primary lymphoma of the central nervous system (CNS) or known lymphomatous involvement of the CNS. CNS imaging and cerebrospinal fluid sampling are not mandatory in the absence of a clinical suspicion of lymphomatous involvement of the CNS.
- •Current infection with HIV, Hepatitis B or Hepatitis C. Patients will have serologic testing performed during screening for HIV and Hepatitis B and C. Any serologic results suggestive of an ongoing viral infection will be further investigated as necessary to clarify the patient's status.
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of CPI-0610, including any unresolved nausea, vomiting, or diarrhea that is CTCAE grade >
- •Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- •Acute myocardial infarction or angina pectoris ≤ 6 months prior to starting study drug
- •Serum cardiac troponin (cTn) level ≥ 99% percentile of the upper reference limit
- •QTcF > 470 msec on the screening ECG
- •Left ventricular ejection fraction (LVEF) < 40%
- •Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded.)
- •Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
- •Systemic anti-cancer treatment or radiotherapy less than 2 weeks before the first dose of CPI-0610
- •Radioimmunotherapy (e.g., 131I-tositumomab, 90Y-ibritumomab tiuxetan) less than 6 weeks before the first dose of CPI-0610
- •Treatment with an investigational small molecule less than 2 weeks before the first dose of CPI-
- •In addition, the first dose of CPI-0610 should not occur before a period equal to or greater than 5 half-lives of the small molecule investigational agent has elapsed.
- •Treatment with a therapeutic antibody less than 4 weeks before the first dose of CPI-
- •A minimum 2-week period between the last treatment with a therapeutic antibody and the first dose of CPI-0610 may be permitted in patients with rapidly progressive or aggressive subtypes of lymphoma following discussion with the medical monitor.
- •Treatment with medications that are known to be strong inhibitors or inducers of CYP450 enzymes.
- •Treatment with medications that are known to carry a risk of Torsades de Pointes.
- •Immunosuppressive treatment that cannot be discontinued both prior to study entry and for the duration of the study. Oral prednisone at a dose of 10 mg or less per day is allowed, as are other oral corticosteroids given at glucocorticoid-equivalent doses. Topical, nasal and inhaled corticosteroids are also allowed.
- •Pregnant or lactating women
- •Women of child-bearing potential and men with reproductive potential, if they are unwilling to use adequate contraception while on study therapy and for 3 months thereafter
- •Patients unwilling or unable to comply with this study protocol
研究组 & 干预措施
CPI-0610
Experimental
干预措施: CPI-0610 (Drug)
结局指标
主要结局
Frequency of dose-limiting toxicities (DLTs) associated with CPI-0610 administration during the first cycle (first 21 days) of treatment
时间窗: DLTs asessed during Cycle 1 (first 21 days on study)
次要结局
- Pharmacodynamic effects of CPI-0610: Changes in the expression of MYC and other genes in tumor tissue; changes in cellular proliferation and in the extent of apoptosis; changes in tumor metabolism(Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1)
- Safety and tolerability of CPI-0610 as assessed by: frequency of adverse events and serious adverse events; changes in hematology and clinical chemistry values; changes in physical examination, vital signs, electrocardiogram, ECHO and ECOG score(Assessed from Day 1 of Cycle 1 through 30 days after patient's last dose of study drug)
- Pharmacokinetic parameters of CPI-0610: AUC(0-t), AUC(0-inf), AUCtau,ss, Tmax, Cmax, Ctrough, T1/2, Vd/F, CL/F(Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1)
- Changes in the expression of a set of genes in peripheral blood mononuclear cells (PBMCs) that are sensitive to BET inhibition(Assessed during cycle 1 (first 21 days on study))
- Anti-lymphoma activity associated with CPI-0610 treatment(After every 2 cycles of treatment for the first 6 cycles, and after every 4 cycles thereafter; assessed up to approximately 12 months)
研究者
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