A Study to Evaluate the Efficacy of Venetoclax Monotherapy in Relapsed/Refractory Participants With Chronic Lymphocytic Leukemia (CLL)

Open-Label, Single Arm, Phase 3b, Multi-Center Study Evaluating the Efficacy of Venetoclax (ABT 199) in Relapsed/Refractory Subjects With Chronic Lymphocytic Leukemia (CLL)

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.

Following the Screening period, all eligible participants initiate venetoclax on a once daily (QD) dosing schedule. To mitigate the risk for tumor lysis syndrome (TLS), dosing will start with a 5-week dose titration phase.

Participants may receive venetoclax for up to 2 years provided they continue to tolerate the drug, have no evidence of disease progression (based on investigator assessment), do not have unacceptable toxicity and do not meet any of the criteria for subject discontinuation. In countries where venetoclax is not commercially available, participants who continued to derive benefit after 2 years of treatment may extend their treatment for up to 2 additional years in an extended access phase. Participants in the extended access phase of this study who continue to derive benefit from venetoclax after the 2-year extension and are transferring to the venetoclax extension study, Study M19-388 (NCT03844048), may remain in Extended Access for up to 1 additional year or until the extension study is approved and initiated at the site, whichever is sooner.

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