A Study of the Efficacy of ABT-199 in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia With the 17p Deletion
Condition: Chronic Lymphocytic Leukemia; 17p Deletion; Cancer of the Blood and Bone Marrow
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      This was an open-label, multicenter, global study to determine the efficacy of ABT-199
      (Venetoclax) monotherapy in participants with relapsed/refractory (R/R) or previously
      untreated chronic lymphocytic leukemia (CLL) harboring 17p deletion.
    

Detailed description: 
      This study was designed to enroll approximately 150 participants in 2 cohorts: a main cohort
      of approximately 100 participants, and a safety expansion (SE) cohort of approximately 50
      participants. The primary objective of the main cohort was to evaluate the efficacy of
      ABT-199 monotherapy in participants with R/R CLL harboring the 17p deletion. The primary
      objective of the safety expansion cohort was to evaluate the safety of ABT-199 in
      approximately 50 participants with R/R CLL harboring 17p deletion treated per updated tumor
      lysis syndrome (TLS) prophylaxis and management measures.
    

Intervention name(s): ABT-199 (Main Cohort); ABT-199 (Safety Expansion Cohort)
Intervention type(s): Drug; Drug
Intervention description(s): Participants received a test dose of ABT-199 of ≤ 20 mg on Week 1 Day 1 of the Lead-In Period. For those with significant electrolyte and/or lymphocyte changes within 24 hours of the first dose, the 20 mg dose was maintained for 7 days with escalation to 50 mg on Week 2 Day 1. If none of the electrolyte and/or lymphocyte changes occurred within 24 hours from ABT-199 20 mg dose administration, the participant was dose-escalated to 50 mg on Week 1 Day 2. After the first dose of 50 mg, if no laboratory abnormalities occurred, the participant remained on the 50 mg dose through Week 1. After receiving the 50 mg dose for approximately 1 week (6 to 7 days), the following dose escalation proceeded with weekly increases in dose: → 100 mg → 200 mg → 400 mg (or additional lead-in steps to designated 400 mg dose), as tolerated.; Participants received an initial dose of ABT-199 of 20 mg on Week 1 Day 1 of the Lead-In Period. If one or more electrolyte changes (from the 0 hr measurement prior to dosing) suggestive of laboratory tumor lysis syndrome (LTLS) or clinical TLS (CTLS) occurred within 24 hours of the 20 mg dose, no additional doses were administered until resolution. Upon resolution of laboratory abnormalities, the 20 mg dose was continued through Week 1. If no significant findings suggestive of clinical or laboratory TLS occurred within 24 hours, the 20 mg dose was continued through Week 1 Day 7, and escalated to a dose of 50 mg on Week 2 Day 1. Those who had drug interruptions may have been allowed to escalate to and be maintained at 50 mg for 1 week after they had been on a 20 mg dose for at least 1 week (5 - 7 days). After a week at 50 mg, weekly dose escalations were implemented as follows: 100 mg → 200 mg → 400 mg (or additional lead-in steps to designated 400 mg dose) as tolerated.
Other intervention name(s): Venetoclax; GDC-0199; Venetoclax; GDC-0199
Intervention MeSH terms: Venetoclax
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic Lymphocytic Leukemia; 17p Deletion