Safety and Efficacy of PCI-32765 in Participants With Relapsed/Refractory Mantle Cell Lymphoma (MCL)
Condition: Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: PCI-32765
Intervention description: 560 mg daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 115.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pharmacyclics; Mantle; Mantle Cell; Lymphoma; Non-Hodgkins; Bortezomib; Velcade; Naive; PCYC

Summary:

      The primary objective of this study was to evaluate the efficacy of ibrutinib in participants
      with relapsed or refractory MCL.

      The secondary objective was to evaluate the safety of a fixed daily dosing regimen (560 mg
      daily) of PCI-32765 in this population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women ≥ 18 years of age

          -  ECOG performance status of ≤ 2

          -  Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1
             or t(11;14), and measurable disease on cross sectional imaging that is ≥ 2 cm in the
             longest diameter and measurable in 2 perpendicular dimensions

          -  Documented failure to achieve at least partial response (PR) with, or documented
             disease progression disease after, the most recent treatment regimen

          -  At least 1, but no more than 5, prior treatment regimens for MCL (Note: Subjects
             having received ≥2 cycles of prior treatment with bortezomib, either as a single agent
             or as part of a combination therapy regimen, will be considered to be
             bortezomib-exposed.)

          -  Willing and able to participate in all required evaluations and procedures in this
             study protocol including swallowing capsules without difficulty

          -  Ability to understand the purpose and risks of the study and provide signed and dated
             informed consent and authorization to use protected health information (in accordance
             with national and local subject privacy regulations)

        Major exclusion criteria:

          -  Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer
             antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation
             therapy within 3 weeks, or major surgery within 2 weeks of first dose of study drug

          -  Any life-threatening illness, medical condition or organ system dysfunction which, in
             the investigator's opinion, could compromise the subject's safety, interfere with the
             absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue
             risk

          -  Clinically significant cardiovascular disease such as uncontrolled or symptomatic
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
             screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart
             Association Functional Classification

          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel or ulcerative colitis, symptomatic
             inflammatory bowel disease, or partial or complete bowel obstruction

          -  Any of the following laboratory abnormalities:

               1. Absolute neutrophil count (ANC) < 750 cells/mm3 (0.75 x 109/L) unless there is
                  documented bone marrow involvement

               2. Platelet count < 50,000 cells/mm3 (50 x 109/L) independent of transfusion support
                  unless there is documented bone marrow involvement

               3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0
                  x upper limit of normal (ULN)

               4. Creatinine > 2.0 x ULN