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.
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. III. To evaluate assessment of bone marrow biopsy, and possible correlation between complete response (CR) vs. bone marrow biopsy assessment (e.g., clear of infiltration of leukemic cells accordingly to morphology, and/or negative on leukemic cells according to immunohistochemistry). IV. To evaluate safety of the CPI-613 + bendamustine + rituximab combination. OUTLINE: This is a dose-escalation study of 6,8-bis(benzylthio)octanoic acid. 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. After completion of study treatment, patients are followed up every 2 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, United States
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)
Will be accomplished by monitoring toxicities and using the dose escalation plan.
Time frame: 4 weeks
Response rate assessed by the modified IWG criteria
The response rate and its 95% confidence interval will be assessed.
Time frame: Up to 2 years
Disease control rate assessed by the modified IWG criteria
The DCR and its 95% confidence interval will be assessed.
Time frame: Up to 2 years
Overall survival assessed by the modified IWG criteria
OS curves will be plotted using Kaplan-Meier methods.
Time frame: Up to 2 years
Progression free survival assessed by the modified IWG criteria
PFS curves will be plotted using Kaplan-Meier methods and median PFS will be examined.
Time frame: Up to 2 years
Bone marrow biopsy analysis
Evaluation of bone marrow and possible correlation between CR vs. bone marrow biopsy assessments such as clear of infiltration of leukemic cells accordingly to morphology, and/or negative on leukemic cells according to immunohistochemistry. Correlations will be estimated to examine the relationship between results from bone marrow biopsies and response and time to event results.
Time frame: Baseline
Incidence of toxicities graded according to NCI CTCAE
Will be examined by looking at each toxicity identified earlier in the protocol by grade.
Time frame: Up to 6 courses
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