Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)
Condition: B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: PCI-32765
Intervention description: 420 mg daily
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoma, B-Cell; Leukemia, Lymphoid; Leukemia, B-Cell; Bruton's Tyrosine Kinase

Summary:

      The purpose of this study is to establish the safety of orally administered PCI-32765 in
      combination with fludarabine/cyclophosphamide/rituximab (FCR) and bendamustine/rituximab (BR)
      in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma(SLL).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed CLL or SLL and satisfying at least 1 of the following
             criteria for requiring treatment:

               -  Progressive splenomegaly and/or lymphadenopathy identified by physical
                  examination or radiographic studies

               -  Anemia (<11 g/dL) or thrombocytopenia (<100,000/μL) due to bone marrow
                  involvement

               -  Presence of unintentional weight loss > 10% over the preceding 6 months

               -  NCI CTCAE Grade 2 or 3 fatigue

               -  Fevers > 100.5° or night sweats for > 2 weeks without evidence of infection

               -  Progressive lymphocytosis with an increase of > 50% over a 2 month period or an
                  anticipated doubling time of < 6 months

          2. 1 to 3 prior treatment regimens for CLL/SLL

          3. ECOG performance status of ≤ 1

          4. ≥ 18 years of age

          5. Willing and able to participate in all required evaluations and procedures in this
             study protocol including swallowing capsules without difficulty

          6. 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)

        Exclusion Criteria:

          1. Any chemotherapy, therapeutic antineoplastic antibodies (not including radio- or toxin
             immunoconjugates), radiation therapy, or experimental antineoplastic therapy within 4
             weeks of first dose of study drug

          2. Radio- or toxin-conjugated antibody therapy within 10 weeks of first dose of study
             drug

          3. Concomitant use of medicines known to cause QT prolongation or torsades de pointes

          4. Transformed lymphoma or Richter's transformation 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 PO, or put the study outcomes at undue risk

          5. Any of the following laboratory abnormalities: oAbsolute neutrophil count (ANC) < 1000
             cells/mm3 (1.0 x 109/L) oPlatelet count < 50,000/mm3 (50 x 109/L) oSerum aspartate
             transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of
             normal (ULN) oCreatinine > 2.0 x ULN or creatinine clearance < 40 mL/min