Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or Indolent Non-Hodgkin's Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Splenic Marginal Zone Lymphoma
Drug: BTK inhibitor PCI-32765
Drug: bendamustine hydrochloride
Other: pharmacogenomic studies
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Dose-escalation Trial of Rituxan and Bendamustine in Combination With Bruton's Tyrosine Kinase Inhibitor, PCI-32765, in Patients With Relapsed Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Indolent Non-Hodgkin's Lymphoma|
- 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 [ Time Frame: during first course of therapy ] [ Designated as safety issue: Yes ]MTD is defined as the highest dose Level at which =< 1 of 6 patients experienced a DLT.
- Frequency, severity, and relatedness of adverse events [ Time Frame: up to 30 days after last dose of treatment ] [ Designated as safety issue: Yes ]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.
- Overall response rate [ Time Frame: up to 24 months post treatment ] [ Designated as safety issue: No ]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.
- Duration of response [ Time Frame: up to 24 months post treatment ] [ Designated as safety issue: No ]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.
- Identification of germinal center versus nongerminal center DLCL [ Time Frame: screening or cycle 1 day 1 predose ] [ Designated as safety issue: No ]Determined by immunohistochemistry in patients with DLCL enrolled in the dose escalation portion of the study and in the DLCL expansion cohort.
- Correlation of PGx with response and toxicity [ Time Frame: screening or cycle 1 day 1 predose ] [ Designated as safety issue: No ]Data will be evaluated with pharmacokinetics and clinical outcomes to identify significant associations and potential PGx biomarkers.
|Study Start Date:||December 2011|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor, chemo, monoclonal antibody)
Patients receive BTK inhibitor PCI-32765 PO QD on days 1-28. Patients also receive rituximab 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.
Drug: BTK inhibitor PCI-32765
Other Names:Biological: rituximab
Other Names:Drug: bendamustine hydrochloride
Other Names:Other: pharmacogenomic studies
Other Name: Pharmacogenomic StudyOther: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01479842
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Kristie Blum, MD||Ohio State University|