A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

A Phase 2 Open-Label Study of the Efficacy of Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

This is a Phase 2, open-label, multicenter study, evaluating the efficacy of venetoclax in participants with relapsed or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) either in presence of 17p deletion (Cohort 1) or those who have failed a B-receptor signaling pathway inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status (Cohort 2).

Inclusion Criteria:

• Participant must have a diagnosis of relapsed or refractory chronic lymphocytic leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) that meets 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (iwCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines and the following:

  • Participant must have an indication for treatment according to the 2008 Modified iwCLL NCI-WG Guidelines.
  • SLL participant must have measurable disease (B-lymphocytosis greater than 5 × 10^9/L or an enlarged lymph node(s) (Longest Diameter (LDi) > 1.5 cm at baseline) or hepatomegaly or splenomegaly due to CLL).
  • SLL participant must have presence of lymphadenopathy and absence of cytopenias caused by a clonal marrow infiltrate.
  • Participant must have relapsed or refractory CLL/SLL after receiving at least one prior line of therapy.

• Participants (in Cohort 1) must have 17p deletion, assessed by a central laboratory.

• Participants (in Cohort 2) must meet both of the following:

  • Relapsed/refractory disease to B-Cell Receptor Signaling Pathway Inhibitor (BCRI) treatment;
  • And either of the following: (a) relapsed/refractory disease to chemoimmunotherapy (CIT), or (b) ineligible to receive CIT, defined as having known 17p deletion or TP53 mutation, or Cumulative Illness Rating Scale (CIRS) >6 or calculated creatinine clearance <70 mL/min, or participants in whom the investigator evaluated that the use of CIT was inappropriate.

• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.

• Participant must have adequate bone marrow function, coagulation profile, renal, and hepatic function, per laboratory reference range at Screening.

• No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Exclusion Criteria:

• Participant has undergone an allogeneic stem cell transplant.

• Participant has developed Richter's transformation confirmed by biopsy.

• Participant has prolymphocytic leukemia.

• Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to screening), including autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP).

• Participant has previously received venetoclax or other BCL-2 inhibitors.

• Participant is known to be positive for Human Immunodeficiency Virus (HIV).

• Participant has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.

• Participant has received any of the following within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of venetoclax, or has not recovered to less than Common Toxicity Criteria for Adverse Events (CTCAE) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:

  • Any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy or targeted small molecule agents.
  • Investigational therapy, including targeted small molecule agents.

• Participant has known allergy to both xanthine oxidase inhibitors and rasburicase.