PCI-32765 for Special Cases of Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Condition: Leukemia; Leukemia, Lymphocytyc; CLL (Chronic Lymphocytic Leukemia); SLL (Small Lymphocytic Lymphoma)
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: PCI 32765
Intervention description: 420 mg daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 86.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Treatment; CLL (Chronic Lymphocytic Leukemia); SLL (Small Lymphocytic Lymphoma); Leukemia; Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; CLL; Small Lymphocytic Leukemia; SLL

Summary:

      Background:

      - Chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are types of blood or
      lymph node cancers that mostly affect the elderly. CLL/SLL both create abnormal white blood
      cells that hurt the immune system and make it more difficult to fight infections. These
      cancers are usually diagnosed after age 50; more than half of the people with CLL/SLL are
      over age 70. Elderly people often do not respond well to standard chemotherapy for CLL/SLL.
      They may have other health problems that make chemotherapy difficult. In addition,
      individuals who have a genetic abnormality called 17p deletion also do not respond well to
      standard treatments for CLL/SLL. Researchers want to test a new cancer treatment drug,
      PCI-32765, to see if it can treat CLL/SLL in these hard-to-treat groups.

      Objectives:

      - To see if PCI-32765 is a safe and effective treatment for CLL/SLL in older people and
      people with 17p deletion.

      Eligibility:

        -  Individuals over 65 years of age who have CLL/SLL.

        -  Individuals at least 18 years of age who have CLL/SLL and 17p deletion.

      Design:

        -  Participants will be screened with a medical history, physical exam, and imaging
           studies. Blood and urine samples will be taken. Optional bone marrow and lymph node
           biopsies may also be taken.

        -  Participants will take PCI-32765 capsules every day for 28 days (one cycle of
           treatment). Treatment will be monitored with frequent blood tests and clinic visits.

        -  PCI-32765 will be given for six cycles of treatment. Those who benefit from the drug
           will continue to take it as long as there are no side effects and the disease does not
           progress. Those who do not benefit will stop treatment and have regular followup exams.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Cohort 1: Treated and untreated patients age 65 or older and need for therapy

             Cohort 2: Treated (maximum accrual n=16) and untreated (n=27, evaluable) patients at
             least 18 years old with 17p deletion or p53 expression by immunohistochemistry or p53
             mutation by sequencing analysis.

          2. Men and women with histologically confirmed disease as defined by the following:

               -  B-lymphocytosis greater than 5000 cells/microL (may be less than 5000
                  cells/microL if lymphadenopathy is present with histologic confirmation of lymph
                  node involvement by SLL)

               -  Immunophenotypic profile read by an expert pathologist as consistent with CLL.
                  This will include CD5, CD19, and CD20 expression by the CLL cells typically also
                  with CD23 expression, but CD23 negative cases may be included if there is no
                  t11;14 translocation present.

          3. Active disease as defined by at least one of the following:

               -  Weight loss greater than or equal to 10% within the previous 6 months

               -  Extreme fatigue

               -  Fevers of greater than 100.5 degrees F for greater than or equal to 2 weeks
                  without evidence of infection

               -  Night sweats for more than one month without evidence of infection

               -  Evidence of progressive marrow failure as manifested by the development of, or
                  worsening of, anemia and/or thrombocytopenia

               -  Massive or progressive splenomegaly

               -  Massive nodes or clusters or progressive lymphadenopathy

               -  Progressive lymphocytosis with an increase of greater than 50% over a 2 month
                  period, or an anticipated doubling time of less than 6 months

               -  Compensated autoimmune hemolysis

          4. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
             2

          5. ANC greater than 500/microL, platelets greater than 30,000/microL

          6. Agreement to use contraception during the study and for 90 days after the last dose of
             study drug if sexually active and able to bear children

          7. Willing and able to participate in all required evaluations and procedures in this
             study protocol including swallowing capsules without difficulty

          8. 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. Previous radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or
             treatment with an investigational product fpr CCL treatement in the last 4 weeks (i.e.
             intravenous immunoglobulin).

          2. Transformed CLL

          3. Autoimmune hemolytic anemia or thrombocytopenia requiring steroid therapy

          4. Impaired hepatic function: Total bilirubin greater than or equal to 1.5 times upper
             limit of normal unless dute to Gilbert's disease, AST/ ALT greater than or equal to
             2.5 times institutional upper limit of normal unless due to infiltration of the liver.

          5. Impaired renal funtion: Creatinine greater than or equal to 2.0 mg/dL or GFR less than
             or equal to 50ml/min

          6. 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

          7. Concomitant immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages
             equivalent to prednisone > 20 mg/day), or experimental therapy

          8. Active Hepatitis B infection

          9. HIV infection

         10. Female patients: Current pregnancy or unwilling to take oral contraceptives or refrain
             from pregnancy if of childbearing potential or currently breastfeeding. Male patients
             who are unwilling to follow the contraception requirements described in this protocol.

         11. Psychiatric illness/social situations that would limit the patient s ability to
             tolerate and/or comply with study requirements.

         12. Unable to understand the investigational nature of the study or give informed consent.

         13. Individuals < 18 yrs old

         14. Known hypersensitivity to any component of PCI-32765

         15. Any prior therapy with PCI 32765 or any other BTK inhibitors.

         16. Requires anticoagulation with warfarin.

         17. Requires treatment with strong CY3A4/5 and/or CYP2D6 inhibitors (unless no alternative
             is available).