A Phase 2 Open-Label Study of the Efficacy and Safety of ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia (CLL) Subjects With Relapse or Refractory to B-Cell Receptor Signaling Pathway Inhibitor Therapy
1 other identifier
interventional
127
1 country
15
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2014
Longer than P75 for phase_2
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 12, 2014
CompletedFirst Posted
Study publicly available on registry
May 19, 2014
CompletedStudy Start
First participant enrolled
September 10, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 22, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 22, 2021
CompletedResults Posted
Study results publicly available
December 19, 2022
CompletedDecember 19, 2022
November 1, 2022
7.3 years
May 12, 2014
November 18, 2022
November 18, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR)
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.
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
Secondary Outcomes (4)
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
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
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
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
Other Outcomes (2)
Time to Next Anti-Chronic Lymphocytic Leukemia Treatment (TNNT)
Collected every 3 months for a period of 5 years after the last participant had enrolled into the study
Percentage of Participants With Minimal Residual Disease (MRD) Negativity Status
Assessed at Week 24, Day 1; after the first Complete Response, Complete Remission with Incomplete Marrow Recovery, or Partial Response; at 12-week interval visits until two consecutive negative MRD levels were reported
Study Arms (4)
ABT-199 after ibrutinib therapy
EXPERIMENTALParticipants 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.
ABT-199 after idelalisib therapy
EXPERIMENTALParticipants 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.
ABT-199 after ibrutinib therapy: Expansion Cohort
EXPERIMENTALParticipants 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.
ABT-199 after idelalisib therapy: Expansion Cohort
EXPERIMENTALParticipants 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.
Interventions
Each dose of venetoclax was to be taken with approximately 240 mL of water within 30 minutes after the completion of breakfast or the participant's first meal of the day.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AbbVielead
- Roche-Genentechcollaborator
Study Sites (15)
Moores Cancer Center at UC San Diego /ID# 128535
La Jolla, California, 92093, United States
University of California, Los Angeles /ID# 127262
Los Angeles, California, 90095, United States
Stanford University School of Med /ID# 126495
Stanford, California, 94305-2200, United States
Georgetown University Hospital /ID# 127261
Washington D.C., District of Columbia, 20007, United States
Emory Midtown Infectious Disease Clinic /ID# 131249
Atlanta, Georgia, 30322, United States
Northwestern University Feinberg School of Medicine /ID# 126497
Chicago, Illinois, 60611-2927, United States
Beth Israel Deaconess Medical Center /ID# 134509
Boston, Massachusetts, 02215-5400, United States
Dana-Farber Cancer Institute /ID# 126496
Boston, Massachusetts, 02215, United States
Columbia Univ Medical Center /ID# 128536
New York, New York, 10032-3725, United States
New York Presbyterian Hospital Weill Cornell Medical Center /ID# 129648
New York, New York, 10032-3725, United States
Univ Rochester Med Ctr /ID# 130011
Rochester, New York, 14642, United States
The Ohio State University /ID# 127263
Columbus, Ohio, 43210, United States
University of Pennsylvania /ID# 126860
Philadelphia, Pennsylvania, 19104-5502, United States
University of Texas MD Anderson Cancer Center /ID# 126498
Houston, Texas, 77030, United States
University of Utah /ID# 130813
Salt Lake City, Utah, 84112-5500, United States
Related Publications (3)
Roberts AW, Ma S, Kipps TJ, Coutre SE, Davids MS, Eichhorst B, Hallek M, Byrd JC, Humphrey K, Zhou L, Chyla B, Nielsen J, Potluri J, Kim SY, Verdugo M, Stilgenbauer S, Wierda WG, Seymour JF. Efficacy of venetoclax in relapsed chronic lymphocytic leukemia is influenced by disease and response variables. Blood. 2019 Jul 11;134(2):111-122. doi: 10.1182/blood.2018882555. Epub 2019 Apr 25.
PMID: 31023700DERIVEDCoutre S, Choi M, Furman RR, Eradat H, Heffner L, Jones JA, Chyla B, Zhou L, Agarwal S, Waskiewicz T, Verdugo M, Humerickhouse RA, Potluri J, Wierda WG, Davids MS. Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy. Blood. 2018 Apr 12;131(15):1704-1711. doi: 10.1182/blood-2017-06-788133. Epub 2018 Jan 5.
PMID: 29305552DERIVEDJones JA, Mato AR, Wierda WG, Davids MS, Choi M, Cheson BD, Furman RR, Lamanna N, Barr PM, Zhou L, Chyla B, Salem AH, Verdugo M, Humerickhouse RA, Potluri J, Coutre S, Woyach J, Byrd JC. Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol. 2018 Jan;19(1):65-75. doi: 10.1016/S1470-2045(17)30909-9. Epub 2017 Dec 12.
PMID: 29246803DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Medical Services
- Organization
- AbbVie
Study Officials
- STUDY DIRECTOR
ABBVIE INC.
AbbVie
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
May 12, 2014
First Posted
May 19, 2014
Study Start
September 10, 2014
Primary Completion
December 22, 2021
Study Completion
December 22, 2021
Last Updated
December 19, 2022
Results First Posted
December 19, 2022
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
- Access Criteria
- Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.