Clinical trial NCT02141282: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: Oncology
Chronic Lymphocytic Leukemia
Cancer of the blood and bone marrow
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Roche-Genentech
First posted: 2014-05-19
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 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:
measure: Duration of Response (DOR)
timeFrame: 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
measure: Time to Progression (TTP)
timeFrame: 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
measure: Progression-free Survival (PFS)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: 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:
measure: Time to Next Anti-Chronic Lymphocytic Leukemia Treatment (TNNT)
timeFrame: Collected every 3 months for a period of 5 years after the last participant had enrolled into the study
measure: Percentage of Participants With Minimal Residual Disease (MRD) Negativity Status
timeFrame: 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
Locations:
city: La Jolla
country: United States
facility: Moores Cancer Center at UC San Diego /ID# 128535
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles /ID# 127262
state: California
city: Stanford
country: United States
facility: Stanford University School of Med /ID# 126495
state: California
city: Washington
country: United States
facility: Georgetown University Hospital /ID# 127261
state: District of Columbia
city: Atlanta
country: United States
facility: Emory Midtown Infectious Disease Clinic /ID# 131249
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 126497
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center /ID# 134509
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 126496
state: Massachusetts
city: New York
country: United States
facility: Columbia Univ Medical Center /ID# 128536
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital Weill Cornell Medical Center /ID# 129648
state: New York
city: Rochester
country: United States
facility: Univ Rochester Med Ctr /ID# 130011
state: New York
city: Columbus
country: United States
facility: The Ohio State University /ID# 127263
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 126860
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 126498
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah /ID# 130813
state: Utah
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
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.
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.
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.