A Study of ACP-196 (Acalabrutinib) in Subjects With Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: ACP-196 (acalabrutinib)
Intervention description: ACP-196 100 mg to be administered orally (PO) twice a day BID.
Intervention MeSH terms: Acalabrutinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Lymphocytic Leukemia; Ibrutinib Intolerant

Summary:

      A Phase 2 Study to evaluate the Efficacy and Safety of ACP-196 (acalabrutinib) in Subjects
      with Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men and women ≥ 18 years of age.

          2. Prior diagnosis of CLL

          3. Must have received ≥ 1 prior therapy for CLL

          4. Intolerant of ibrutinib

          5. Documented disease progression after stopping ibrutinib therapy as defined by the
             IWCLL 2008 criteria

          6. Willing and able to participate in all required evaluations and procedures in this
             study protocol including swallowing capsules without difficulty.

          7. ECOG performance status of ≤ 2.

        Exclusion Criteria:

          1. Ongoing AE attributed to ibrutinib therapy

          2. Treatment with systemic anticancer therapy for CLL is prohibited between
             discontinuation of ibrutinib and enrollment on this trial.

          3. Prior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT- 199)

          4. Prior malignancy (other than CLL), except for adequately treated basal cell or
             squamous cell skin cancer, in situ cancer, or other cancer from which the subject has
             been disease free for ≥ 2 years.

          5. Significant cardiovascular disease such as uncontrolled or symptomatic untreated
             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, or QTc > 480 msec at screening. Exception:
             Subjects with controlled, asymptomatic atrial fibrillation during screening are
             allowed to enroll on study.

          6. Malabsorption syndrome, disease significantly affecting gastrointestinal function,
             resection of the stomach, extensive small bowel resection that is likely to affect
             absorption, symptomatic inflammatory bowel disease, partial or complete bowel
             obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.

          7. Evidence of active Richter's transformation or any evidence of disease progression on
             ibrutinib therapy or any BTK inhibitor.

          8. CNS involvement by CLL or related Richter's transformation.

          9. Known history of human immunodeficiency virus (HIV), serologic status reflecting
             active hepatitis B or C infection, or any uncontrolled active systemic infection.

         10. Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura
             (ITP)

         11. History of stroke or intracranial hemorrhage within 2 months before the first dose of
             study drug.

         12. History of bleeding diathesis.

         13. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before
             screening.

         14. Major surgical procedure within 28 days of first dose of study drug.

         15. Requires treatment with a strong CYP3A inhibitor