Trial Information

A Phase 1 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Subjects With Recurrent Mature B-Cell Neoplasms

This is an open-label (all people know the identity of the intervention), multicenter (study
conducted at multiple sites), dose escalation study. The study consists of 3 phases,
including, the screening phase (within 14 days prior to the first study medication), the
treatment phase, and the follow up phase. In the treatment phase, patients with recurrent
mature B-cell neoplasms will be divided into 2 cohorts: Cohort 1 (consisting patients
between 3 and 12), and Cohort 2 (consisting patients between 6 and 12). Cohort 1 will be
further divided into 2 phases: a single dose (SD) phase and a multiple dose (MD) phase.
During the initial SD phase, patients will first receive a single dose of PCI-32765 at 140
mg. After a washout period (period when the participant is not receiving any study
medication) of between 72 and 168 hours, patients will then receive a second single dose of
PCI-32765 at 280 mg. Following a second washout period, patients will enter the MD phase,
where they will receive PCI-32765 at multiple doses of 420 mg per day for 35 days during the
first cycle (35 days in Cycle 1) and for 28 days during the second cycle (28 days in Cycle
2) and every cycle thereafter. In cohort 2, patients will receive multiple doses of 560 mg
per day for 35 days in Cycle 1, 28 days in Cycle 2, and every cycle thereafter. The
patient's registration in Cohort 2 will be started after tolerability of Cohort 1 is
confirmed. Tolerability of each dose level will be evaluated based on the dose-limiting
toxicity (DLT) occurrence rate in Cycle 1 of each Cohort. Safety evaluations for adverse
events, clinical laboratory tests, electrocardiogram, vital signs, Eastern Cooperative
Oncology Group (ECOG) performance status, physical examination, and corneal eye examination
will be monitored throughout the study.