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

AbbVie

Status and phase: Completed; Phase 2

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: Venetoclax

Study type: Interventional

Funder types: Industry

Identifiers

NCT02141282

M14-032

Details and patient eligibility

About

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.

Enrollment: 127 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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127 participants in 4 patient groups

ABT-199 after ibrutinib therapy

Experimental group

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.

Treatment:

Drug: Venetoclax

ABT-199 after idelalisib therapy

Experimental group

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.

Treatment:

Drug: Venetoclax

ABT-199 after ibrutinib therapy: Expansion Cohort

Experimental group

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.

Treatment:

Drug: Venetoclax

ABT-199 after idelalisib therapy: Expansion Cohort

Experimental group

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.

Treatment:

Drug: Venetoclax