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

AbbVie

Status and phase: Enrolling; Phase 2

Conditions: Small Lymphocytic Lymphoma (SLL); Chronic Lymphocytic Leukemia (CLL)

Treatments: Drug: Venetoclax

Study type: Interventional

Funder types: Industry

Identifiers

NCT02966756

M14-728

Details and patient eligibility

About

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).

Enrollment: 110 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 2 patient groups

Cohort 1: Venetoclax

Experimental group

Description:

Participants with 17p deletion status will receive various doses of venetoclax once daily (QD).

Treatment:

Drug: Venetoclax

Cohort 2: Venetoclax

Experimental group

Description:

Participants who have failed a B-Cell Receptor Signaling Pathway Inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status will receive various doses of venetoclax once daily (QD).

Treatment:

Drug: Venetoclax