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
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
during first course of therapy
Kristie Blum, MD
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|