TriangleNCT02141282 · CITED IN SOURCE DOCUMENTS
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
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2022-12-19
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Overall Response Rate (ORR)
Duration of Response (DOR)
Time to Progression (TTP)
Progression-free Survival (PFS)
Overall Survival (OS)
Time to Next Anti-Chronic Lymphocytic Leukemia Treatment (TNNT)
Percentage of Participants With Minimal Residual Disease (MRD) Negativity Status
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- maximum Age
- 99 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- 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.
- intervention Names
- Drug: Venetoclax
- label
- ABT-199 after ibrutinib therapy
- type
- EXPERIMENTAL
- 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.
- intervention Names
- Drug: Venetoclax
- label
- ABT-199 after idelalisib therapy
- type
- EXPERIMENTAL
- 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.
- intervention Names
- Drug: Venetoclax
- label
- ABT-199 after ibrutinib therapy: Expansion Cohort
- type
- EXPERIMENTAL
- 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 Names
- Drug: Venetoclax
- label
- ABT-199 after idelalisib therapy: Expansion Cohort
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- ABT-199 after ibrutinib therapy
- ABT-199 after ibrutinib therapy: Expansion Cohort
- ABT-199 after idelalisib therapy
- ABT-199 after idelalisib therapy: Expansion Cohort
- 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.
- name
- Venetoclax
- other Names
- ABT-199
- VENCLEXTA®
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 127
- type
- ACTUAL
Registered outcome plans (not posted results)
- other Outcomes
- 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.
- measure
- Time to Next Anti-Chronic Lymphocytic Leukemia Treatment (TNNT)
- time Frame
- Collected every 3 months for a period of 5 years after the last participant had enrolled into the study
- description
- The rate of MRD response is defined as the percentage of participants who had MRD negative status.
- measure
- Percentage of Participants With Minimal Residual Disease (MRD) Negativity 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
- primary Outcomes
- 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.
- measure
- 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
- secondary Outcomes
- 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.
- measure
- Duration of Response (DOR)
- 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
- 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.
- measure
- Time to Progression (TTP)
- 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
- 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.
- measure
- Progression-free Survival (PFS)
- 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
- 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.
- measure
- Overall Survival (OS)
- 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
Full 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.
Source references
- references
- 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.
- pmid
- 31023700
- type
- DERIVED
- 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.
- pmid
- 29305552
- type
- DERIVED
- 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.
- pmid
- 29246803
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-8339a09e3e2c51e73981
- requested nct id
- NCT02141282
- primary nct id
- NCT02141282
- source kind
- fda_spl_label
- source record id
- 5d893369-497c-46ee-9b64-ee737fab4225
- source file sha256
- bbaf8e3e49a06d91fa717d034adb1798932735c99e42d8d769cf5f9eb31d345e
- payload sha256
- 9511b1f74eec9cad1a06b7edbc9b344510c7bca1761dbadaae11028d6a993f60
- payload
- application numbers
- NDA208573
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-8339a09e3e2c51e73981
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT02141282
- occurrences
- context exact
- he ORR was 76% (95% CI: 64%, 86%), with a CR + CRi rate of 10% and PR rate of 66%. The median DOR was 36.2 months (range: 2.4 to 52.4 months). M14-032 M14-032 (NCT02141282) was an open-label, multicenter trial that enrolled patients with CLL who had been previously treated with and progressed on or after ibrutinib or idelalisib.
- end
- 16644
- exact text
- NCT02141282
- start
- 16633
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00300.json
- source file sha256
- bbaf8e3e49a06d91fa717d034adb1798932735c99e42d8d769cf5f9eb31d345e
- source json pointer
- /results/98/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 5d893369-497c-46ee-9b64-ee737fab4225
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- e029d66014882009f1241859331c828e89c4363a558a3916f4f5f0b6a4c1e22b
- spl effective time
- 20260520
- spl set id
- b118a40d-6b56-cee3-10f6-ded821a97018
Preserved source evidence · Not medical advice