Phase I Dose-Escalation Study of CPI-613, in Combination With Bendamustine, in Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Classic Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- MTD of 6,8-bis(benzylthio)octanoic acid when used in combination with bendamustine hydrochloride, defined as the dose level immediately below the dose level that induced a dose-limiting toxicity in < 2 patients
研究概览
简要总结
This phase I trial studies the side effects and best dose of CPI-613 when given together with bendamustine hydrochloride in treating patients with relapsed or refractory T-cell non-Hodgkin lymphoma or Hodgkin lymphoma. CPI-613 may kill cancer cells by turning off their mitochondria, which are used by cancer cells to produce energy and are the building blocks needed to make more cancer cells. By shutting off mitochondria, CPI-613 may deprive the cancer cells of energy and other supplies needed to survive and grow. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CPI-613 with bendamustine hydrochloride may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of CPI-613 [6,8-bis(benzylthio)octanoic acid], when used in combination with bendamustine (bendamustine hydrochloride) in patients with relapsed and refractory classic Hodgkin lymphoma (HL) or T-cell non-Hodgkin lymphoma (NHL) who have or have not received hematopoietic cell transplant.
SECONDARY OBJECTIVES:
I. To evaluate response rate (RR) and disease control rate (DCR), derived from the modified International Work Group (IWG) criteria and International Cutaneous Lymphoma (Olsen criteria) for cutaneous lymphomas.
II. To evaluate overall survival (OS) and progression-free survival (PFS), and possible correlation between RR and DCR derived from modified IWF criteria vs. OS and PFS.
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
- •Histologically or cytologically confirmed T-cell NHL or classic HL (i.e., nodular sclerosis HL, mixed cellularity HL, lymphocyte rich classic HL, and lymphocyte depleted HL) that has relapsed from, or is refractory to, all standard therapies (including autologous transplantation) known to provide clinical benefit, but have not been treated with bendamustine for their lymphoma
- •Must have measurable disease (e.g., a tumor mass > 1 cm)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Expected survival > 3 months
- •Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation
- •Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists
- •At least 2 weeks must have elapsed from any prior surgery
- •Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x upper normal limit (UNL), alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (=< 5 x UNL if liver metastases present)
- •Bilirubin =< 1.5 x UNL
- •Serum creatinine =< 1.5 mg/dL or 133 µmol/L
- •"International normalized ratio" or INR must be =< 1.5
- •No evidence of active infection and no serious infection within the past month
- •Mentally competent, ability to understand and willingness to sign the informed consent form
排除标准
- •Known cerebral metastases, central nervous system (CNS) or epidural tumor
- •Having "currently active" second malignancy unrelated to HL or NHL, unless they have completed anti-cancer therapy, are in complete response and are considered by their physicians to be at less than 30% risk of relapse
- •Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication, within the past 2 weeks prior to initiation of treatment with study drugs
- •Serious medical illness that would potentially increase patients' risk for toxicity
- •Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
- •History of abdominal fistula or gastrointestinal perforation =< 6 months prior to treatment with study drugs
- •Pregnant women, or women of child-bearing potential not using reliable means of contraception
- •Lactating females
- •Fertile men unwilling to practice contraceptive methods during the study period
- •Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
- •Unwilling or unable to follow protocol requirements
- •Active heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction or symptomatic congestive heart failure
- •Patients with a history of myocardial infarction that is < 3 months prior to registration
- •Evidence of active infection, or serious infection within the past month
- •Patients with known human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
- •Patients who have received cancer immunotherapy of any type within the past 2 weeks prior to initiation of CPI-613 treatment
- •Requirement for immediate palliative treatment of any kind including surgery
研究组 & 干预措施
Treatment (CPI-613 and bendamustine hydrochloride)
Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-4 of week 1 and on days 1 and 4 of weeks 2 and 3. Patients also receive bendamustine hydrochloride IV over 30 minutes on days 4 and 5 of week 1. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: 6,8-bis(benzylthio)octanoic acid (Drug)
Treatment (CPI-613 and bendamustine hydrochloride)
Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-4 of week 1 and on days 1 and 4 of weeks 2 and 3. Patients also receive bendamustine hydrochloride IV over 30 minutes on days 4 and 5 of week 1. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: bendamustine hydrochloride (Drug)
结局指标
主要结局
MTD of 6,8-bis(benzylthio)octanoic acid when used in combination with bendamustine hydrochloride, defined as the dose level immediately below the dose level that induced a dose-limiting toxicity in < 2 patients
时间窗: Up to 28 days
Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
次要结局
未报告次要终点