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

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT02141282

Collaborator

Roche-Genentech (Industry)

127

Enrollment

Locations

Arms

87.1

Actual Duration (Months)

8.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, non-randomized, multicenter, Phase 2 study evaluating the efficacy and safety of ABT-199 in approximately 120 subjects with relapsed or refractory CLL after B-cell receptor signaling pathway inhibitors (BCR PI) treatment.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: ABT-199	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

127 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 10, 2014

Actual Primary Completion Date :

Dec 13, 2021

Actual Study Completion Date :

Dec 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABT-199 after ibrutinib therapy Single daily doses increasing weekly as tolerated	Drug: ABT-199 ABT-199 monotherapy
Experimental: ABT-199 after ibrutinib or idelalisib therapy Single daily doses increasing weekly as tolerated	Drug: ABT-199 ABT-199 monotherapy
Experimental: ABT-199 after idelalisib therapy Single daily doses increasing weekly as tolerated	Drug: ABT-199 ABT-199 monotherapy

Arm

Intervention/Treatment

Experimental: ABT-199 after ibrutinib therapy

Single daily doses increasing weekly as tolerated

Drug: ABT-199

ABT-199 monotherapy

Experimental: ABT-199 after ibrutinib or idelalisib therapy

Single daily doses increasing weekly as tolerated

Drug: ABT-199

ABT-199 monotherapy

Experimental: ABT-199 after idelalisib therapy

Single daily doses increasing weekly as tolerated

Drug: ABT-199

ABT-199 monotherapy

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [Measured up to 5 years after the last subject has enrolled in the study.]
To evaluate the efficacy of ABT-199 monotherapy in subjects with chronic lymphocytic leukemia (CLL) relapsed or refractory to B-cell Receptor Signaling Pathway Inhibitors. Assessed by the investigator, based on laboratory results, physical examinations, CT scans, and bone marrow examinations

Secondary Outcome Measures

Duration of response [Measured up to 2 years after the last subject has enrolled in the study.]
The number of days from the date of first response (complete response (CR) or partial response (PR)) to the earliest recurrence or disease progression (PD)
Time to progression (TTP) [Measured up to 5 years after the last subject has enrolled in the study.]
The number of days from the date of first dose or enrollment if not dosed to the date of earliest PD
Overall survival (OS) [Measured up to 5 years after the last subject has enrolled in the study.]
The number of days from the date of first dose to the date of death for all dosed subjects
Progression-free survival (PFS) [Measured up to 5 years after the last subject has enrolled in the study.]
The number of days from the date of first dose to the date of earliest PD or death

Other Outcome Measures

Time to Next Anti-CLL Treatment (TNT) [Measured up to 2 years after the last subject has enrolled in the study.]
The number of days from the date of first dose of ABT-199 to the date of first dose of new non-protocol anti-leukemia therapy (NPT) or death from any cause
Rate of minimal residual disease (MRD) negativity status [Measured up to 2 years after the last subject has enrolled in the study.]
The presence of less that once CLL cell per 10,000 leukocytes in either peripheral blood and/or bone marrow

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject must have a diagnosis of CLL that meets 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (iwCLL NCI-WG) criteria
Subject has relapsed/refractory disease with an indication for treatment
Subject has refractory disease or developed recurrence after therapy with a BCR PI
Subject must have an Eastern Cooperative Oncology Group performance score of equal to or less than 2
Subject must have adequate bone marrow function at Screening
Subject must have adequate coagulation profile, renal, and hepatic function, per laboratory reference range at Screening

Exclusion Criteria:

Subject has undergone an allogeneic stem cell transplant within the past year
Subject has developed Richter's transformation confirmed by biopsy
Subject has active and uncontrolled autoimmune cytopenia
Subject has malabsorption syndrome or other condition that precludes enteral route of administration
Subject is human immunodeficiency virus (HIV) positive or has chronic hepatitis B or hepatitis C virus requiring treatment
Subject has known contraindication or allergy to both xanthine oxidase inhibitors and rasburicase.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moores Cancer Center at UC San Diego /ID# 128535	La Jolla	California	United States	92093
2	University of California, Los Angeles /ID# 127262	Los Angeles	California	United States	90095
3	Stanford University School of Med /ID# 126495	Stanford	California	United States	94305-2200
4	Georgetown University Hospital /ID# 127261	Washington	District of Columbia	United States	20007
5	Winship Cancer Institute of Emory University /ID# 131249	Atlanta	Georgia	United States	30322
6	Northwestern University Feinberg School of Medicine /ID# 126497	Chicago	Illinois	United States	60611-2927
7	Beth Israel Deaconess Medical Center /ID# 134509	Boston	Massachusetts	United States	02215-5400
8	Dana-Farber Cancer Institute /ID# 126496	Boston	Massachusetts	United States	02215
9	Columbia Univ Medical Center /ID# 128536	New York	New York	United States	10032-3725
10	New York Presbyterian Hospital Weill Cornell Medical Center /ID# 129648	New York	New York	United States	10032-3725
11	Univ Rochester Med Ctr /ID# 130011	Rochester	New York	United States	14642
12	The Ohio State University /ID# 127263	Columbus	Ohio	United States	43210
13	University of Pennsylvania /ID# 126860	Philadelphia	Pennsylvania	United States	19104-5502
14	University of Texas MD Anderson Cancer Center /ID# 126498	Houston	Texas	United States	77030
15	University of Utah /ID# 130813	Salt Lake City	Utah	United States	84112-5500