a study of venetoclax in participants with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma

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

Summary: 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).


Eligibility criteria:
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.

Keywords: relapsed chronic lymphocytic leukemia (cll) refractory chronic lymphocytic leukemia (cll) 17p deletion venetoclax leukemia lymphoproliferative disorders small lymphocytic lymphoma (sll) venclexta