Study to Assess Change in Disease Activity and Adverse Events of Oral Venetoclax With Intravenous (IV) Obinutuzumab in Adult Participants With Recurring Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The purpose of this study is to assess retreatment with venetoclax-obinutuzumab (VenG) in participants previously treated with fixed duration first-line (IL) therapy of venetoclax in combination with an anti-CD20 antibody +/- X (where X is any additional drug). 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 cohorts, based on when symptoms of CLL came back after previous treatment in first-line. Approximately 75 adult participants with CLL who have been treated with venetoclax in combination with an anti-CD20 antibody +/- X 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.

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

Conditions
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Chronic Lymphocytic Leukemia (CLL)

Intervention / Treatment
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* Drug: Venetoclax
* Drug: Obinutuzumab


Participation Criteria
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Eligibility Criteria
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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 + anti-CD20 antibody +/- X 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 treatment. Exclusion Criteria: - Received intervening treatment for CLL after completing previous treatment with a venetoclax + anti-CD20 antibody +/- X regimen.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - venetoclax + obinutuzumab<br>Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for six 28-day cycles. | Drug: Venetoclax<br>* Oral tablet<br>* Other names: GDC-0199;Drug: Obinutuzumab<br>* Intravenous (IV) infusion<br>* Other names: Gazyva;|
| Experimental: Cohort 2 - venetoclax + obinutuzumab<br>Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for eighteen 28-day cycles. | Drug: Venetoclax<br>* Oral tablet<br>* Other names: GDC-0199;Drug: Obinutuzumab<br>* Intravenous (IV) infusion<br>* Other names: Gazyva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response (OR) in Cohort 1 after end of combination treatment | OR is defined as the percentage of participants achieving a best response of partial remission (PR), nodular partial remission (nPR), complete remission with incomplete marrow recovery (CRi), or complete remission (CR). Disease assessments will be based on the 2018 International Workshop for Chronic Lymphocytic Leukemia (iwCLL) criteria for tumor response. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OR in Cohort 1 after end of combination treatment | OR rate is defined as the percentage of participants achieving a best response of CR or CRi | 9 months | 
| OR in Cohort 1 after end of treatment | OR is defined as the percentage of participants achieving a best response of PR, nPR, CRi, or CR. Disease assessments will be based on the 2018 iwCLL criteria for tumor response. | 15 months | 
| Time to Response (TTR) in Cohort 1 | TTR is defined as the time from first dose until first response (PR or better). | 15 months | 
| Duration of Response (DOR) in Cohort 1 | DOR is defined as the time from first response (PR or better) until progressive disease (PD) or death. | 15 months | 
| Time to Next Treatment (TTNT) for CLL in Cohort 1 | TTNT is defined as the time from first dose until first dose of a non-protocol anti-CLL therapy. | 15 months | 
| Progression-free Survival (PFS) in Cohort 1 | PFS is defined as the time from first dose until PD or death. | 15 months | 
| Overall Survival (OS) in Cohort 1 | OS is defined as the time from first dose until death. | 15 months | 
| Percentage of Participants with Undetectable Minimal Residual Disease (uMRD) rate (<10^-4) in Cohort 1 after end of combination treatment | Percentage of participants with uMRD rate, measured in peripheral blood. | 9 months | 
| Percentage of Participants with Undetectable Minimal Residual Disease (uMRD) rate (<10^-4) in Cohort 1 after end of treatment | Percentage of participants with uMRD rate, measured in peripheral blood. | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Lymphocytic Leukemia (CLL), Venetoclax, ABT-199, Venclexta, GDC-0199, Obinutuzumab, Gazyva, GA101, Cancer, ReVenG