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

NCT ID: NCT02141282

Last Updated: 2022-12-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-10

Study Completion Date

2021-12-22

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia

Keywords

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Oncology Chronic Lymphocytic Leukemia Cancer of the blood and bone marrow

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ABT-199 after ibrutinib therapy

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.

Group Type EXPERIMENTAL

Venetoclax

Intervention Type DRUG

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.

ABT-199 after idelalisib therapy

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.

Group Type EXPERIMENTAL

Venetoclax

Intervention Type DRUG

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.

ABT-199 after ibrutinib therapy: Expansion Cohort

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.

Group Type EXPERIMENTAL

Venetoclax

Intervention Type DRUG

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.

ABT-199 after idelalisib therapy: Expansion Cohort

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.

Group Type EXPERIMENTAL

Venetoclax

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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ABT-199 VENCLEXTA®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roche-Genentech

INDUSTRY

Sponsor Role collaborator

AbbVie

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

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Moores Cancer Center at UC San Diego /ID# 128535

La Jolla, California, United States

Site Status

University of California, Los Angeles /ID# 127262

Los Angeles, California, United States

Site Status

Stanford University School of Med /ID# 126495

Stanford, California, United States

Site Status

Georgetown University Hospital /ID# 127261

Washington D.C., District of Columbia, United States

Site Status

Emory Midtown Infectious Disease Clinic /ID# 131249

Atlanta, Georgia, United States

Site Status

Northwestern University Feinberg School of Medicine /ID# 126497

Chicago, Illinois, United States

Site Status

Beth Israel Deaconess Medical Center /ID# 134509

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute /ID# 126496

Boston, Massachusetts, United States

Site Status

Columbia Univ Medical Center /ID# 128536

New York, New York, United States

Site Status

New York Presbyterian Hospital Weill Cornell Medical Center /ID# 129648

New York, New York, United States

Site Status

Univ Rochester Med Ctr /ID# 130011

Rochester, New York, United States

Site Status

The Ohio State University /ID# 127263

Columbus, Ohio, United States

Site Status

University of Pennsylvania /ID# 126860

Philadelphia, Pennsylvania, United States

Site Status

University of Texas MD Anderson Cancer Center /ID# 126498

Houston, Texas, United States

Site Status

University of Utah /ID# 130813

Salt Lake City, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 31023700 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29305552 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29246803 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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M14-032

Identifier Type: -

Identifier Source: org_study_id