PCI-32765 (Ibrutinib) in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-cell Prolymphocytic Leukemia
Condition: Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory/Relapsed Chronic Lymphocytic Leukemia
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, B-Cell
Intervention: ibrutinib; Correlative laboratory samples; quality of life assessment
Intervention description: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.; Blood samples will be collected and used for pharmacodynamic testing. Samples will be collected pre-dose on Cycle 1 Day 1 and 2 hours post-dose Cycle 1 Day 1, pre-dose on Day 2 and Day 8 of Cycle 1 and pre-dose on Day 1 of Cycles 2 and 3 and then every 3 cycles thereafter for 1 year (Cycle 15 Day 1). Samples will also be collected at the time of relapse and at any time when bone marrow biopsy is performed.; During screening, sociodemographic information (e.g., age, race, marital status) and reports of recent (last year) stressful events will be obtained. The assessment will consist of measures of emotional distress, depressive symptoms, and quality of life. Quality of life measures will be administered during screening and on Days 1 (±3), 8 (±3),, 15 (±3),, 22 (±3), of Cycle 1, Day 1 (±3), of Cycle 2 and on day 1 (±7) of Cycles 3, 6, and then every 3 months thru month 24.
Intervention MeSH terms: Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 154.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bruton's Tyrosine Kinase; CLL; SLL; B-PLL

Summary:

      This is a Phase II, single institution open-label, non-randomized monotherapy study to
      evaluate the clinical efficacy and durable disease control of PCI-32765 administered to
      patients with relapsed/refractory CLL/SLL/PLL of all risk categories with patients having
      deletion 17p13 independently evaluated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of relapsed/refractory CLL/SLL who require treatment and have
             failed at least one prior therapy.

          -  Patients must have available results of interphase cytogenetics CLL fluorescent in
             situ hybridization (FISH) panel; the cytogenetic analysis must be done prior to
             starting therapy but after any recent therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Life expectancy greater than 2 months

          -  Bilirubin =< 1.5 X the institutional upper limit of normal unless due to Gilbert's
             disease or disease related to Aspartate aminotransferase (AST) or alanine
             aminotransferase (ALT) =< 2.5 X the institutional upper limit of normal unless disease
             related

          -  Creatinine =< 1.5 X the institutional upper limit of normal unless disease related

          -  Absolute neutrophil count (ANC) >= 0.75 X 10^9/L

          -  Platelet count >= 30 X 10^9/L

          -  Agree to use contraception during the study and for 30 days after the last dose of
             study drug if sexually active and able to bear children

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Patients with uncontrolled or active infection requiring antibiotic therapy; patients
             with controlled infections who are receiving extended antibiotics or prophylactic
             therapy are not excluded

        Exclusion Criteria:

          -  Patients who have had chemotherapy, radiotherapy or immunotherapy within 4 weeks prior
             to the first dose of study drug (corticosteroids for disease-related symptoms allowed
             but doses equivalent to > 20 mg prednisone orally per day require 1 week washout
             before study drug administration or steroid dose must be equal to =< 20 mg prednisone
             orally daily)

          -  Patients who have not recovered from adverse events of >= grade 3 toxicity due to
             agents administered more than 4 weeks ago

          -  Receiving any other investigational agents

          -  Previously randomized to any PCI-32765 clinical trial

          -  Known secondary malignancy that limits survival to less than two years

          -  Patients with 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

          -  Patients requiring anti-coagulation with warfarin or other Vitamin K antagonists or
             heparin products including low molecular weight heparin (LMWH)

          -  Currently active, clinically significant hepatic impairment Child-Pugh class B or C
             according to the Child Pugh classification

          -  Patients requiring treatment with a strong cytochrome P450 3A4/5 (CYP3A4/5) and/or
             cytochrome P450 2D6 (CYP2D6) inhibitor

          -  Patients with a 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 PO, or put the study
             outcomes at undue risk

          -  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

          -  Active central nervous system (CNS) involvement by lymphoma

          -  Pregnant or women who are breastfeeding