This phase I trial studies the side effects and best dose of BTK inhibitor PCI-32765 when given together with rituximab and bendamustine hydrochloride in treating patients with recurrent non-Hodgkin lymphoma (NHL). BTK inhibitor PCI-32765 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving BTK inhibitor PCI-32765 together with rituximab and bendamustine hydrochloride may kill more cancer cells.
PRIMARY OBJECTIVES: I. Identify the specific toxicities and a recommended phase 2 dose of PCI-32765 (BTK inhibitor PCI-32765) orally (PO) in combination with rituximab and bendamustine (bendamustine hydrochloride) (i.e., "combination therapy") in patients with relapsed and refractory B-cell NHL. SECONDARY OBJECTIVES: I. Evaluate the activity of combined rituximab, bendamustine, and PCI-32765 in patients with relapsed and refractory B-cell NHL as measured by response rate and duration of response. II. Identify potential marker(s) predictive of response to the combination therapy. III. Correlate pharmacogenetic (PGx) findings with patient response and toxicity. OUTLINE: This is a dose-escalation study of BTK inhibitor PCI-32765. Patients receive BTK inhibitor PCI-32765 PO once daily (QD) on days 1-28. Patients also receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue receiving BTK inhibitor PCI-32765 PO in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 4 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Given PO
Given IV
Given IV
Correlative studies
Correlative studies
Correlative studies
Ohio State University Medical Center
Columbus, Ohio, United States
Maximum tolerated dose (MTD) as determined by the incidence of dose limiting toxicities (DLT) of BTK inhibitor PCI-32765 when given in combination with rituximab and bendamustine hydrochloride
MTD is defined as the highest dose Level at which =\< 1 of 6 patients experienced a DLT.
Time frame: during first course of therapy
Frequency, severity, and relatedness of adverse events
Laboratory shift tables containing counts and percentages will be prepared by treatment assignment, laboratory parameter, and time. Summary tables will be prepared for each laboratory parameter. Figures of changes in laboratory parameters over time will be generated.
Time frame: up to 30 days after last dose of treatment
Overall response rate
The point estimate of the rate will be calculated for the per protocol analysis set. The response rate 95% confidence interval estimates also will be derived. Association between the correlation markers and response will be explored using graphical and descriptive analysis.
Time frame: up to 24 months post treatment
Duration of response
From time measurement criteria are met for complete response(CR)or partial response(PR)until the first date that recurrent or progressive disease occurs. Median duration of overall response will be assessed with 95% confidence interval.
Time frame: up to 24 months post treatment
Identification of germinal center versus nongerminal center DLCL
Determined by immunohistochemistry in patients with DLCL enrolled in the dose escalation portion of the study and in the DLCL expansion cohort.
Time frame: screening or cycle 1 day 1 predose
Correlation of PGx with response and toxicity
Data will be evaluated with pharmacokinetics and clinical outcomes to identify significant associations and potential PGx biomarkers.
Time frame: screening or cycle 1 day 1 predose
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