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

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02141282
• Other study ID #: M14-032
• Status: Completed
• Phase: Phase 2
• Start date: September 10, 2014
• Est. completion date: December 22, 2021

Study information

• Verified date: November 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: December 22, 2021
• Est. primary completion date: December 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• Venetoclax
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.

Locations

Country	Name	City	State
United States	Emory Midtown Infectious Disease Clinic /ID# 131249	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center /ID# 134509	Boston	Massachusetts
United States	Dana-Farber Cancer Institute /ID# 126496	Boston	Massachusetts
United States	Northwestern University Feinberg School of Medicine /ID# 126497	Chicago	Illinois
United States	The Ohio State University /ID# 127263	Columbus	Ohio
United States	University of Texas MD Anderson Cancer Center /ID# 126498	Houston	Texas
United States	Moores Cancer Center at UC San Diego /ID# 128535	La Jolla	California
United States	University of California, Los Angeles /ID# 127262	Los Angeles	California
United States	Columbia Univ Medical Center /ID# 128536	New York	New York
United States	New York Presbyterian Hospital Weill Cornell Medical Center /ID# 129648	New York	New York
United States	University of Pennsylvania /ID# 126860	Philadelphia	Pennsylvania
United States	Univ Rochester Med Ctr /ID# 130011	Rochester	New York
United States	University of Utah /ID# 130813	Salt Lake City	Utah
United States	Stanford University School of Med /ID# 126495	Stanford	California
United States	Georgetown University Hospital /ID# 127261	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Roche-Genentech

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to Next Anti-Chronic Lymphocytic Leukemia Treatment (TNNT)	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.	Collected every 3 months for a period of 5 years after the last participant had enrolled into the study
Other	Percentage of Participants With Minimal Residual Disease (MRD) Negativity Status	The rate of MRD response is defined as the percentage of participants who had MRD negative 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
Primary	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	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.	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	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.	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	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.	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	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.	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

External Links

•   clinical study report synopsis