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)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia (CLL)
• Intervention / Treatment: Drug: Venetoclax; Drug: Obinutuzumab

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital /ID# 229898
  • Victoria
    • Epping, Victoria, Australia, 3076
      • Active, not recruiting
      • Northern Hospital Epping /ID# 229847
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Ctr /ID# 254634
• Austria
  • Salzburg, Austria, 5020
    • Recruiting
    • Landeskrankenhaus Salzburg-Universitaetsklinikum der PMU (LKH) /ID# 230015
  • Wien, Austria, 1140
    • Recruiting
    • Hanusch Krankenhaus /ID# 230010
  • Niederoesterreich
    • Sankt Poelten, Niederoesterreich, Austria, 3100
      • Recruiting
      • Universitaetsklinikum St. Poelten /ID# 243493
  • Oberoesterreich
    • Linz, Oberoesterreich, Austria, 4010
      • Recruiting
      • Ordensklinikum Linz GmbH Barmherzige Schwestern /ID# 249516
  • Wien
    • Vienna, Wien, Austria, 1090
      • Recruiting
      • Medizinische Universitaet Wien /ID# 230013
    • Vienna, Wien, Austria, 1160
      • Active, not recruiting
      • Klinik Ottakring /ID# 230019
• Brazil
  • Sao Paulo, Brazil, 01236-030
    • Active, not recruiting
    • Instituto de Ensino e Pesquisas Sao Lucas /ID# 243659
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Recruiting
      • Hospital de Clinicas de Porto Alegre /ID# 243657
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 01409-001
      • Active, not recruiting
      • Hospital Nove de Julho /ID# 243658
• Bulgaria
  • Vratsa, Bulgaria, 3000
    • Recruiting
    • MHAT Hristo Botev /ID# 229687
• Germany
  • Berlin, Germany, 10707
    • Recruiting
    • Onkologische Schwerpunktpraxis /ID# 245465
  • Berlin, Germany, 13353
    • Recruiting
    • Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 248748
  • Bremen, Germany, 28239
    • Recruiting
    • DIAKO Ev. Diakonie-Krankenhaus gemeinnuetzige GmbH /ID# 230238
  • Essen, Germany, 45147
    • Recruiting
    • Universitaetsklinikum Essen /ID# 230181
  • Halle (Saale), Germany, 06120
    • Recruiting
    • Universitaetsklinikum Halle (Saale) /ID# 245350
  • Hamburg, Germany, 22081
    • Recruiting
    • OncoResearch Lerchenfeld GmbH /ID# 230191
  • Homburg, Germany, 66424
    • Recruiting
    • Universitaetsklinikum des Saarlandes /ID# 248747
  • Landshut, Germany, 84034
    • Recruiting
    • Klinikum Landshut AdöR der Stadt Landshut /ID# 242991
  • Muenchen, Germany, 80804
    • Completed
    • Muenchen Klinik Schwabing /ID# 230197
  • Paderborn, Germany, 33098
    • Active, not recruiting
    • Bruederkrankenhaus St. Josef Paderborn /ID# 230177
  • Rostock, Germany, 18057
    • Recruiting
    • Universitaetsmedizin Rostock /ID# 230190
  • Baden-Wuerttemberg
    • Mutlangen, Baden-Wuerttemberg, Germany, 73557
      • Recruiting
      • Stauferklinikum Schwaebisch Gmuend /ID# 230176
    • Ulm, Baden-Wuerttemberg, Germany, 89081
      • Active, not recruiting
      • Universitaetsklinikum Ulm /ID# 230164
  • Bayern
    • Landshut, Bayern, Germany, 84036
      • Recruiting
      • VK&K Studien GbR /ID# 230198
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Active, not recruiting
      • Universitaetsklinikum Koeln /ID# 230296
  • Sachsen-Anhalt
    • Dresden, Sachsen-Anhalt, Germany, 01307
      • Active, not recruiting
      • Gemeinschaftspraxis Haematologie - Onkologie BAG /ID# 230168
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Active, not recruiting
      • Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 230186
• Israel
  • H_efa
    • Haifa, H_efa, Israel, 4941492
      • Recruiting
      • Rabin Medical Center /ID# 243220
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • Recruiting
      • The Chaim Sheba Medical Center /ID# 243219
    • Tel Aviv, Tel-Aviv, Israel, 6423906
      • Active, not recruiting
      • Tel Aviv Sourasky Medical Center /ID# 243218
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 91120
      • Recruiting
      • Hadassah /ID# 245059
• Italy
  • Terni, Italy, 05100
    • Recruiting
    • Azienda Ospedaliera Santa Maria Terni /ID# 229442
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • Recruiting
      • AOU Citta della Salute e della Scienza di Torino /ID# 229504
• Romania
  • Bucuresti
    • Bucharest, Bucuresti, Romania, 022328
      • Recruiting
      • Institutul Clinic Fundeni /ID# 241614
• Spain
  • Madrid, Spain, 28006
    • Recruiting
    • Hospital Universitario de la Princesa /ID# 229665
• United States
  • California
    • La Jolla, California, United States, 92093
      • Active, not recruiting
      • Moores Cancer Center at UC San Diego /ID# 230157
  • Iowa
    • Des Moines, Iowa, United States, 50309-1423
      • Recruiting
      • Des Moines Oncology Research Association /ID# 232606
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute /ID# 230061
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System /ID# 230268
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Recruiting
      • St. Luke's Hospital of Duluth /ID# 250021
  • New Jersey
    • Florham Park, New Jersey, United States, 07932-1049
      • Recruiting
      • Summit Medical Group-Florham Park /ID# 244782
    • Hackensack, New Jersey, United States, 07601-7015
      • Recruiting
      • Regional Cancer Care Associates /ID# 244620
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health Presbyterian Medical Center /ID# 230201
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Novant Health Forsyth Medical Center /ID# 249533
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin-Madiso /ID# 232612

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / 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 Names: Gazyva; 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 Names: Gazyva; GA101

What is the study measuring?

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
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
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
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

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: F. Hoffmann-La Roche Ltd; German CLL Study Group (GCLLSG); Dana-Farber Cancer Institute
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related info

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2022
• Primary Completion (Estimated): February 22, 2025
• Study Completion (Estimated): July 23, 2027

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Venetoclax; Chronic Lymphocytic Leukemia (CLL); ABT-199; Venclexta; GDC-0199; Obinutuzumab; GA101; ReVenG; Gazyva
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Antineoplastic Agents, Immunological; Venetoclax; Obinutuzumab
• Other Study ID Numbers: M20-356; 2021-001037-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing 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/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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