A Study to Evaluate the Efficacy of Venetoclax Monotherapy in Relapsed/Refractory Participants With Chronic Lymphocytic Leukemia (CLL)
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Venetoclax
Intervention description: Tablets for oral administration
Intervention MeSH terms: Venetoclax
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 258.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Oncology; Chronic Lymphocytic Leukemia; 17p Deletion; TP53 Mutation; Relapsed; Refractory; B-Cell receptor inhibitor

Summary:

      The purpose of this study is to evaluate the efficacy of venetoclax monotherapy in
      participants with relapsed/refractory CLL with or without the 17p deletion or TP53 mutation,
      including those who have received prior treatment with a B-cell receptor inhibitor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant has Eastern Cooperative Oncology Group (ECOG) performance score of less
             than or equal to 2

          -  Participant has relapsed/refractory disease (received at least 1 prior therapy)

          -  Participant has diagnosis of CLL that meets published 2008 Modified International
             Workshop for Chronic Lymphocytic Leukemia National Cancer Institute Working Group
             (IWCLL NCI-WG) Guidelines and:

               -  has an indication for treatment according to the 2008 Modified IWCLL NCI-WG
                  criteria

               -  has clinically measurable disease (lymphocytosis greater than 5 × 10^9/L and/or
                  palpable and measurable nodes by physical exam and/or organomegaly assessed by
                  physical exam)

          -  In addition, participants:

               -  with or without 17p deletion or TP53 mutation, assessed by a local laboratory in
                  bone marrow or peripheral blood are eligible

               -  may have been previously treated with a prior B-cell receptor inhibitor

          -  Participant must have adequate bone marrow function, coagulation profile, renal, and
             hepatic function, per laboratory at Screening

        Exclusion Criteria:

          -  Participant has developed Richter's transformation or Prolymphocytic leukemia

          -  Participant has previously received venetoclax

          -  History of active malignancies other than CLL within the past 2 years prior to first
             dose of venetoclax, with the exception of:

               -  adequately treated in situ carcinoma of the cervix uteri

               -  adequately treated basal cell carcinoma or localized squamous cell carcinoma of
                  the skin

               -  previous malignancy confined and surgically resected (or treated with other
                  modalities) with curative intent

          -  Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to
             Screening), including autoimmune hemolytic anemia and idiopathic thrombocytopenic
             purpura despite low dose corticosteroids

          -  Participant has undergone an allogeneic stem cell transplant

          -  Treatment with any of the following within five half-lives or 14 days (if half-life
             unknown) as applicable prior to the first dose of venetoclax, or clinically
             significant adverse effect(s)/toxicity(s) of the previous therapy have not resolved to
             < National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
             v4.03 Grade 2:

               -  Any anti-cancer therapy including chemotherapy, or radiotherapy;

               -  Investigational therapy, including targeted small molecule agents

          -  Participant is human immunodeficiency virus (HIV) positive

          -  Participant has known allergy to both xanthine oxidase inhibitors and rasburicase