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) (ReVenG)

• ClinicalTrials.gov Identifier: NCT04895436
• Recruitment Status: Recruiting
• First Posted: May 20, 2021
• Last Update Posted: May 6, 2024
• Sponsor: AbbVie
• Collaborator: F. Hoffmann-La Roche Ltd; German CLL Study Group (GCLLSG); Dana-Farber Cancer Institute
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: May 19, 2021
• First Posted Date: May 20, 2021
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: March 28, 2022
• Estimated Primary Completion Date: February 22, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2023)

Overall response (OR) in Cohort 1 after end of combination treatment [ Time Frame: 9 months ]

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.

Original Primary Outcome Measures (submitted: May 19, 2021)

Overall response rate (ORR) in Cohort 1 after end of combination treatment [ Time Frame: 9 months ]

Overall response rate 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.

Current Secondary Outcome Measures (submitted: June 22, 2023)

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

Original Secondary Outcome Measures (submitted: May 19, 2021)

• CR rate in Cohort 1 after end of combination treatment [ Time Frame: 9 months ]
  CR rate is defined as the percentage of participants achieving a best response of CR or CRi
• CR Rate in Cohort 1 after end of treatment [ Time Frame: 15 months ]
  CR rate is defined as the percentage of participants achieving a best response of CR or CRi.
• ORR in Cohort 1 after end of treatment [ Time Frame: 15 months ]
  ORR 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.
• Time to Response (TTR) in Cohort 1 [ Time Frame: 15 months ]
  TTR is defined as the time from first dose until first response (PR or better).
• Duration of Response (DOR) in Cohort 1 [ Time Frame: 15 months ]
  DOR is defined as the time from first response (PR or better) until progressive disease (PD) or death.
• Time to Next Treatment (TTNT) for CLL in Cohort 1 [ Time Frame: 15 months ]
  TTNT is defined as the time from first dose until first dose of a non-protocol anti-CLL therapy.
• Progression-free Survival (PFS) in Cohort 1 [ Time Frame: 15 months ]
  PFS is defined as the time from first dose until PD or death.
• Overall Survival (OS) in Cohort 1 [ Time Frame: 15 months ]
  OS is defined as the time from first dose until death.
• Percentage of Participants with Undetectable Minimal Residual Disease (uMRD) rate (10^-4) in Cohort 1 after end of combination treatment [ Time Frame: 9 months ]
  Percentage of participants with uMRD rate, measured in peripheral blood.
• Percentage of Participants with Undetectable Minimal Residual Disease (uMRD) rate (10^-4) in Cohort 1 after end of treatment [ Time Frame: 15 months ]
  Percentage of participants with uMRD rate, measured in peripheral blood.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Lymphocytic Leukemia (CLL)

Intervention

• Drug: Venetoclax
  Oral tablet
  Other Names:

  • Venclexta
  • ABT-199
  • GDC-0199
• Drug: Obinutuzumab
  Intravenous (IV) infusion
  Other Names:

  • GA101
  • Gazyva

Study Arms

• Experimental: Cohort 1 - venetoclax + obinutuzumab
  Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for six 28-day cycles.
  Interventions:

  • Drug: Venetoclax
  • Drug: Obinutuzumab
• Experimental: Cohort 2 - venetoclax + obinutuzumab
  Participants will receive venetoclax + obinutuzumab for six 28-day cycles followed by venetoclax for eighteen 28-day cycles.
  Interventions:

  • Drug: Venetoclax
  • Drug: Obinutuzumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 19, 2021): 75
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 28, 2029
• Estimated Primary Completion Date: February 22, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Australia, Austria, Brazil, Bulgaria, Germany, Israel, Italy, Romania, Spain, United States
• Removed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT04895436
• Other Study ID Numbers: M20-356; 2021-001037-39 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: F. Hoffmann-La Roche Ltd; German CLL Study Group (GCLLSG); Dana-Farber Cancer Institute

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: May 2024