Phase I Dose-Escalation Study of CPI-613, in Combination With Bendamustine and Rituximab, in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- MTD of 6,8-bis(benzylthio)octanoic acid, when used in combination with bendamustine hydrochloride and rituximab determined by dose-limiting toxicities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
研究概览
简要总结
This phase I trial studies the side effects and best dose of CPI-613 (6,8-bis[benzylthio]octanoic acid) when given together with bendamustine hydrochloride and rituximab in treating patients with B-cell non-Hodgkin lymphoma that has come back or has not responded to treatment. Drugs used in chemotherapy, such as 6,8-bis(benzylthio)octanoic acid and 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. Monoclonal antibodies, such as rituximab, may find cancer cells and help kill them. Giving 6,8-bis(benzylthio)octanoic acid with bendamustine hydrochloride and rituximab may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of CPI-613, when used in combination with bendamustine (bendamustine hydrochloride) and rituximab in patients with relapsed or refractory B-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.
II. To evaluate overall survival (OS) and progression-free-survival (PFS), and possible correlation between RR and DCR derived from the modified IWG 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 and cytologically confirmed B-cell NHL 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]) and alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 3 x upper normal limit (UNL) (=< 5 x UNL if liver metastases present)
- •Bilirubin =< 1.5 x UNL
- •Serum creatinine =< 1.5 mg/dL or 133 umol/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 Hodgkin lymphoma (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, bendamustine hydrochloride, rituximab)
Patients receive 6,8-bis(benzylthio)octanoic acid intravenously IV over 2 hours on days 1-4 (week 1) and days 1 and 4 (weeks 2 and 3). Patients also receive bendamustine hydrochloride IV over 30 minutes on days 4 and 5 and rituximab on day 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, bendamustine hydrochloride, rituximab)
Patients receive 6,8-bis(benzylthio)octanoic acid intravenously IV over 2 hours on days 1-4 (week 1) and days 1 and 4 (weeks 2 and 3). Patients also receive bendamustine hydrochloride IV over 30 minutes on days 4 and 5 and rituximab on day 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)
Treatment (CPI-613, bendamustine hydrochloride, rituximab)
Patients receive 6,8-bis(benzylthio)octanoic acid intravenously IV over 2 hours on days 1-4 (week 1) and days 1 and 4 (weeks 2 and 3). Patients also receive bendamustine hydrochloride IV over 30 minutes on days 4 and 5 and rituximab on day 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: rituximab (Biological)
Treatment (CPI-613, bendamustine hydrochloride, rituximab)
Patients receive 6,8-bis(benzylthio)octanoic acid intravenously IV over 2 hours on days 1-4 (week 1) and days 1 and 4 (weeks 2 and 3). Patients also receive bendamustine hydrochloride IV over 30 minutes on days 4 and 5 and rituximab on day 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: laboratory biomarker analysis (Other)
结局指标
主要结局
MTD of 6,8-bis(benzylthio)octanoic acid, when used in combination with bendamustine hydrochloride and rituximab determined by dose-limiting toxicities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
时间窗: 4 weeks
Will be accomplished by monitoring toxicities and using the dose escalation plan.
次要结局
- Response rate assessed by the modified IWG criteria(Up to 2 years)
- Disease control rate assessed by the modified IWG criteria(Up to 2 years)
- Overall survival assessed by the modified IWG criteria(Up to 2 years)
- Progression free survival assessed by the modified IWG criteria(Up to 2 years)
- Bone marrow biopsy analysis(Baseline)
- Incidence of toxicities graded according to NCI CTCAE(Up to 6 courses)