Title
A Multicenter, Open-Label, Phase 2 Study to Evaluate the Efficacy and Safety of Venetoclax- Obinutuzumab Retreatment in Patients with Recurring Chronic Lymphocytic Leukemia

Description
Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The purpose of this study is to assess how well venetoclax + obinutuzumab (VenG) works and how safe they are in adult participants with CLL who were previously treated with VenG. Adverse events and change in disease activity will be assessed.

Venetoclax is an approved drug for the treatment of CLL. Study doctors put the participants in 1 of 2 groups, called treatment arms, based on when symptoms of CLL came back after previous treatment with VenG. Approximately 75 adult participants with CLL who have been treated with VenG will be enrolled in the study in approximately 60 sites worldwide.

Participants will receive intravenous (IV) obinutuzumab + oral venetoclax (VenG) in 28-day cycles for a total of 6 cycles per cohort, followed by 6 to 18 cycles of venetoclax alone, for a total treatment of 12 to 24 cycles, depending on the cohort.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Objective
Primary:
The primary objective of the study is to assess the efficacy of VenG retreatment in Cohort 1.

The corresponding primary estimand is the overall response rate (ORR) achieved by "all treated subjects" in Cohort 1 by their end of combination therapy (EOCT) assessment (i.e., EOCT + 3 months, or "EOCT + 3"). See Section 3.2 for additional details about the primary endpoint.

There is no formal hypothesis testing framework being implemented in this study; the study aims only to provide point and interval estimates for ORR.

Secondary:
The secondary efficacy objective is to quantify the efficacy of treatment with VenG in Cohort 1 via the secondary endpoints specified in Section 3.3 below.

No hypothesis testing framework or any formal statistical comparisons will be conducted during this study. Appropriate summaries including descriptive statistics and confidence intervals will serve as the basis for our analysis. See Section 7 for additional details.

Assessing the safety of retreatment with VenG is also a secondary objective of this study.

Treatment Experimental: Cohort 1 - venetoclax + obinutuzumab
Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for six 28-day cycles.
Drug: Venetoclax
Oral tablet
Other Names:
Venclexta
ABT-199
GDC-0199
Drug: Obinutuzumab
Intravenous (IV) infusion
Other Name: GA101

Experimental: Cohort 2 - venetoclax + obinutuzumab
Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for eighteen 28-day cycles.
Drug: Venetoclax
Oral tablet
Other Names:
Venclexta
ABT-199
GDC-0199
Drug: Obinutuzumab
Intravenous (IV) infusion
Other Name: GA101

Key Eligibility Inclusion Criteria:

Documented diagnosis of chronic lymphocytic leukemia (CLL) that requires treatment for CLL according to International Workshop for Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria.

Previously completed venetoclax + obinutuzumab (VenG) regimen as a fixed duration first-line (1L) therapy and achieved documented response, defined as complete remission, complete remission with incomplete marrow recovery, partial remission, or nodular partial remission.

More than 24 months (Cohort 1) or 12-24 months (Cohort 2) have elapsed between last dose of venetoclax and disease progression after completion of 1L VenG treatment.

Received intervening treatment for CLL after previous treatment with VenG.

Applicable Disease Sites
Leukemia

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital