Back to resultsA 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
Primary Purpose
Chronic Lymphocytic Leukemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring Oncology, Chronic Lymphocytic Leukemia, Cancer of the blood and bone marrow
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
Sites / Locations
- Moores Cancer Center at UC San Diego /ID# 128535
- University of California, Los Angeles /ID# 127262
- Stanford University School of Med /ID# 126495
- Georgetown University Hospital /ID# 127261
- Emory Midtown Infectious Disease Clinic /ID# 131249
- Northwestern University Feinberg School of Medicine /ID# 126497
- Beth Israel Deaconess Medical Center /ID# 134509
- Dana-Farber Cancer Institute /ID# 126496
- Columbia Univ Medical Center /ID# 128536
- New York Presbyterian Hospital Weill Cornell Medical Center /ID# 129648
- Univ Rochester Med Ctr /ID# 130011
- The Ohio State University /ID# 127263
- University of Pennsylvania /ID# 126860
- University of Texas MD Anderson Cancer Center /ID# 126498
- University of Utah /ID# 130813
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
ABT-199 after ibrutinib therapy
ABT-199 after idelalisib therapy
ABT-199 after ibrutinib therapy: Expansion Cohort
ABT-199 after idelalisib therapy: Expansion Cohort
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Duration of Response (DOR)
DOR is defined as the number of days from the date of first response (complete response [CR], complete response with incomplete marrow recovery [CRi], nodular partial remission [nPR], or partial remission [PR]) to the earliest recurrence or progressive disease. DOR was analyzed by Kaplan-Meier (K-M) methodology.
Time to Progression (TTP)
TTP is defined as the number of days from the date of first dose to the date of earliest disease progression (PD).
TTP was analyzed by Kaplan-Meier (K-M) methodology.
Progression-free Survival (PFS)
PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (PD) or death. PFS was analyzed by Kaplan-Meier methodology.
Overall Survival (OS)
OS is defined as the number of days from the date of first dose to the date of death for all dosed participants. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later. OS was estimated using Kaplan-Meier methodology.
Full Information
NCT ID
NCT02141282
First Posted
May 12, 2014
Last Updated
November 18, 2022
Sponsor
AbbVie
Collaborators
Roche-Genentech
1. Study Identification
Unique Protocol Identification Number
NCT02141282
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
September 10, 2014 (Actual)
Primary Completion Date
December 22, 2021 (Actual)
Study Completion Date
December 22, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Roche-Genentech
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
Keywords
Oncology, Chronic Lymphocytic Leukemia, Cancer of the blood and bone marrow
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
127 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABT-199 after ibrutinib therapy
Arm Type
Experimental
Arm Description
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.
Arm Title
ABT-199 after idelalisib therapy
Arm Type
Experimental
Arm Description
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.
Arm Title
ABT-199 after ibrutinib therapy: Expansion Cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
ABT-199 after idelalisib therapy: Expansion Cohort
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199, VENCLEXTA®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
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
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
DOR is defined as the number of days from the date of first response (complete response [CR], complete response with incomplete marrow recovery [CRi], nodular partial remission [nPR], or partial remission [PR]) to the earliest recurrence or progressive disease. DOR was analyzed by Kaplan-Meier (K-M) methodology.
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
Title
Time to Progression (TTP)
Description
TTP is defined as the number of days from the date of first dose to the date of earliest disease progression (PD).
TTP was analyzed by Kaplan-Meier (K-M) methodology.
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
Title
Progression-free Survival (PFS)
Description
PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (PD) or death. PFS was analyzed by Kaplan-Meier methodology.
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
Title
Overall Survival (OS)
Description
OS is defined as the number of days from the date of first dose to the date of death for all dosed participants. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later. OS was estimated using Kaplan-Meier methodology.
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
Other Pre-specified Outcome Measures:
Title
Time to Next Anti-Chronic Lymphocytic Leukemia Treatment (TNNT)
Description
TNNT is defined as the number of days from the date of the first dose of venetoclax to the date of first dose of any non-protocol anti-leukemia therapy (NPT) or death from any cause. For participants who did not take NPT, their data was censored at the last known date to be free of NPT. TTNT was analyzed by Kaplan-Meier methodology.
Time Frame
Collected every 3 months for a period of 5 years after the last participant had enrolled into the study
Title
Percentage of Participants With Minimal Residual Disease (MRD) Negativity Status
Description
The rate of MRD response is defined as the percentage of participants who had MRD negative status.
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Moores Cancer Center at UC San Diego /ID# 128535
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
University of California, Los Angeles /ID# 127262
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford University School of Med /ID# 126495
City
Stanford
State/Province
California
ZIP/Postal Code
94305-2200
Country
United States
Facility Name
Georgetown University Hospital /ID# 127261
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Emory Midtown Infectious Disease Clinic /ID# 131249
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine /ID# 126497
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611-2927
Country
United States
Facility Name
Beth Israel Deaconess Medical Center /ID# 134509
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215-5400
Country
United States
Facility Name
Dana-Farber Cancer Institute /ID# 126496
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Columbia Univ Medical Center /ID# 128536
City
New York
State/Province
New York
ZIP/Postal Code
10032-3725
Country
United States
Facility Name
New York Presbyterian Hospital Weill Cornell Medical Center /ID# 129648
City
New York
State/Province
New York
ZIP/Postal Code
10032-3725
Country
United States
Facility Name
Univ Rochester Med Ctr /ID# 130011
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
The Ohio State University /ID# 127263
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pennsylvania /ID# 126860
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104-5502
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center /ID# 126498
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah /ID# 130813
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112-5500
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
IPD Sharing 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/
IPD Sharing URL
https://vivli.org/ourmember/abbvie/
Citations:
PubMed Identifier
31023700
Citation
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.
Results Reference
derived
PubMed Identifier
29305552
Citation
Coutre 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.
Results Reference
derived
PubMed Identifier
29246803
Citation
Jones 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.
Results Reference
derived
Links:
URL
https://www.abbvieclinicaltrials.com/study/?id=M14-032&Latitude=&Longitude=&LocationName=#additional-resources-section
Description
clinical study report synopsis
Learn more about this trial
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
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