A Phase 2 Open-Label Study of the Efficacy and Safety of ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia Subjects With Relapse or Refractory to B-Cell Receptor Signaling Pathway Inhibitor Therapy
Overview
- Phase
- Phase 2
- Intervention
- Venetoclax
- Conditions
- Chronic Lymphocytic Leukemia
- Sponsor
- AbbVie
- Enrollment
- 127
- Locations
- 15
- Primary Endpoint
- Overall Response Rate (ORR)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This was an open-label, non-randomized, multicenter, Phase 2 study evaluating the efficacy and safety of ABT-199 in 127 participants with relapsed or refractory chronic lymphocytic leukemia (CLL) after B-cell receptor signaling pathway inhibitors (BCR PI) treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant must have a diagnosis of chronic lymphocytic leukemia (CLL) that meets 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (IWCLL NCI-WG) criteria
- •Participant has relapsed/refractory disease with an indication for treatment
- •Participant has refractory disease or developed recurrence after therapy with a B-cell receptor pathway inhibitor (BCR PI)
- •Participant must have an Eastern Cooperative Oncology Group performance score of ≤ 2
- •Participant must have adequate bone marrow function at Screening
- •Participant must have adequate coagulation profile, renal, and hepatic function, per laboratory reference range at Screening
Exclusion Criteria
- •Participant has undergone an allogeneic stem cell transplant within the past year
- •Participant has developed Richter's transformation confirmed by biopsy
- •Participant has active and uncontrolled autoimmune cytopenia
- •Participant has malabsorption syndrome or other condition that precludes enteral route of administration
- •Participant is human immunodeficiency virus (HIV) positive or has chronic hepatitis B or hepatitis C virus requiring treatment
- •Participant has known contraindication or allergy to both xanthine oxidase inhibitors and rasburicase
Arms & Interventions
ABT-199 after ibrutinib therapy
Participants with ibrutinib-resistant or refractory chronic lymphocytic leukemia (CLL) received venetoclax tablets once daily (QD) until disease progression or study drug discontinuation; median time on treatment was 593 days. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.
Intervention: Venetoclax
ABT-199 after idelalisib therapy
Participants with idelalisib-resistant or refractory chronic lymphocytic leukemia (CLL) received venetoclax tablets once daily (QD) until disease progression or study drug discontinuation; median time on treatment was 1023 days. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.
Intervention: Venetoclax
ABT-199 after ibrutinib therapy: Expansion Cohort
Participants with ibrutinib-resistant or refractory chronic lymphocytic leukemia (CLL) received venetoclax tablets once daily (QD) until disease progression or study drug discontinuation; median time on treatment was 622 days. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg. Participants enrolled into the Expansion Cohort with bulky disease at study entry who were non-responders or those who showed signs of clinical progression after completing the ramp up to 400 mg either by clinical disease assessment or by CT/MRI scan between Week 6 to Week 12 may have been permitted to escalate venetoclax to a daily dose of 600 mg.
Intervention: Venetoclax
ABT-199 after idelalisib therapy: Expansion Cohort
Participants with idelalisib-resistant or refractory chronic lymphocytic leukemia (CLL) received venetoclax tablets once daily (QD) until disease progression or study drug discontinuation; median time on treatment was 1189 days. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg. Participants enrolled into the Expansion Cohort with bulky disease at study entry who were non-responders or those who showed signs of clinical progression after completing the ramp up to 400 mg either by clinical disease assessment or by CT/MRI scan between Week 6 to Week 12 may have been permitted to escalate venetoclax to a daily dose of 600 mg.
Intervention: Venetoclax
Outcomes
Primary Outcomes
Overall Response Rate (ORR)
Time Frame: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort
Overall response rate is defined as the percentage of participants with an overall response (per the investigator assessment) 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) criteria.
Secondary Outcomes
- Time to Progression (TTP)(At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort)
- Overall Survival (OS)(At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort)
- Duration of Response (DOR)(At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort)
- Progression-free Survival (PFS)(At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort)