A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL)

April 6, 2026 updated by: AbbVie

A Prospective, Open-Label, Phase IIb/III Study to Evaluate the Risk of TLS and Optimization of the Initiation of Venetoclax in Combination With Obinutuzumab or Acalabrutinib With Different Ramp- Up Periods in Previously Untreated Subjects With CLL

Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The purpose of this study is to assess the safety of venetoclax in combination with obinutuzumab or acalabrutinib in the treatment of CLL. Adverse events and change in disease activity will be assessed.

Venetoclax in combination with obinutuzumab or acalabrutinib is being investigated in the treatment of CLL. Study doctors put the participants in 1 of 4 groups, called treatment arms. Participants will receive oral venetoclax in combination with intravenously (IV) infused obinutuzumab or oral acalabrutinib at in different dosing schemes as part of treatment. Approximately 170 adult participants with CLL who are being treated with venetoclax will be enrolled in the study in approximately 80 sites worldwide.

Participants in Arm A will receive oral venetoclax in combination with IV infused obinutuzumab, with a 5 week venetoclax ramp up. Participants in Arm B will receive oral venetoclax in combination with oral acalabrutinib, with a 5 week venetoclax ramp up. Participants in Arm C and Arm D will receive oral venetoclax in combination with oral acalabrutinib, with differing venetoclax ramp up periods. The total study duration is approximately 28 months.

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

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

170

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
      • Waratah, New South Wales, Australia, 2298
        • Recruiting
        • Calvary Mater Newcastle /ID# 267408
    • Queensland
      • Townsville, Queensland, Australia, 4814
        • Recruiting
        • Townsville University Hospital /ID# 266954
    • Victoria
      • Fitzroy, Victoria, Australia, 3065
        • Recruiting
        • St Vincent's Hospital - Melbourne /ID# 270027
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Recruiting
        • Royal Perth Hospital /ID# 266906
  • France
      • Orléans, France, 45067
        • Recruiting
        • Centre Hospitalier Régional d'Orléans - Hôpital de la Source /ID# 266272
    • Moselle
      • Metz, Moselle, France, 57085
        • Recruiting
        • Centre Hospitalier Régional Metz Thionville - Hôpital de Mercy /ID# 266852
    • Paris
      • Créteil, Paris, France, 94010
        • Recruiting
        • Hopitaux Universitaires Henri Mondor - Hopital Henri Mondor /ID# 266270
      • Paris, Paris, France, 75679
        • Recruiting
        • Hopitaux Universitaires Paris Centre-Hopital Cochin /ID# 267438
    • Pays de la Loire Region
      • St-Priest-en-Jarez, Pays de la Loire Region, France, 42270
        • Recruiting
        • Centre Hospitalier Universitaire de Saint Etienne - Hopital Nord /ID# 266319
    • Provence-Alpes-Côte d'Azur Region
      • Nice, Provence-Alpes-Côte d'Azur Region, France, 06189
        • Recruiting
        • Centre Antoine-Lacassagne /ID# 266894
    • Pyrenees-Atlantiques
      • Bayonne, Pyrenees-Atlantiques, France, 64109
        • Recruiting
        • Centre Hospitalier de la Côte Basque /ID# 266847
    • Savoie
      • Chambéry, Savoie, France, 73007
        • Recruiting
        • Centre Hospitalier Métropole Savoie - Site Hôpital de Chambéry /ID# 266854
    • Somme
      • Amiens, Somme, France, 80054
        • Recruiting
        • CHU Amiens-Picardie Site Sud /ID# 266849
    • Île-de-France Region
      • Argenteuil, Île-de-France Region, France, 95107
        • Recruiting
        • Centre Hospitalier d Argenteuil Victor Dupouy /ID# 266322
  • Greece
    • Achaia
      • Pátrai, Achaia, Greece, 26443
        • Recruiting
        • Olympion General Clinic /ID# 266819
    • Attica
      • Athens, Attica, Greece, 10676
        • Recruiting
        • Evangelismos Hospital /ID# 266815
      • Athens, Attica, Greece, 11527
        • Recruiting
        • General Hospital of Athens Laiko /ID# 266813
      • Athens, Attica, Greece, 12462
        • Recruiting
        • University General Hospital Attikon /ID# 266814
    • Evros
      • Alexandroupoli, Evros, Greece, 68100
        • Recruiting
        • University General Hospital of Alexandroupoli /ID# 266816
  • Puerto Rico
      • Rio Piedras, Puerto Rico, 00935
        • Recruiting
        • Pan American Center for Oncology Trials /ID# 266243
  • Serbia
      • Novi Sad, Serbia, 21000
        • Recruiting
        • University Clinical Center Vojvodina /ID# 266674
    • Beograd
      • Belgrade, Beograd, Serbia, 11080
        • Recruiting
        • Clinical Hospital Center - Bežanijska Kosa /ID# 266567
      • Belgrade, Beograd, Serbia, 11000
        • Recruiting
        • University Clinical Center Serbia /ID# 266579
      • Belgrade, Beograd, Serbia, 11000
        • Recruiting
        • Clinical Hospital Center Zvezdara /ID# 266560
    • Nisavski Okrug
      • Niš, Nisavski Okrug, Serbia, 18300
        • Recruiting
        • University Clinical Center Nis /ID# 266580
    • Sumadijski Okrug
      • Kragujevac, Sumadijski Okrug, Serbia, 34000
        • Recruiting
        • University Clinical Center Kragujevac /ID# 266568
    • Vojvodina
      • Kamenitz, Vojvodina, Serbia, 21208
        • Recruiting
        • Institute for Oncology of Vojvodina /ID# 266556
  • Spain
      • Madrid, Spain, 28033
        • Recruiting
        • Hospital MD Anderson Cancer Center Madrid /ID# 267167
      • Madrid, Spain, 28027
        • Recruiting
        • CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 266969
      • Seville, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocio /ID# 266968
    • A Coruna
      • Santiago de Compostela, A Coruna, Spain, 15706
        • Recruiting
        • Complejo Hospitalario Universitario de Santiago (CHUS) /ID# 267164
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Recruiting
        • Hospital Universitario Puerta de Hierro - Majadahonda /ID# 266967
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra - Pamplona /ID# 267762
  • Taiwan
      • Taichung, Taiwan, 40447
        • Recruiting
        • China Medical University Hospital /ID# 267018
      • Taipei, Taiwan, 100
        • Recruiting
        • National Taiwan University Hospital /ID# 267017
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Linkou Chang Gung Memorial Hospital /ID# 267045
    • Kaohsiung
      • Kaohsiung City, Kaohsiung, Taiwan, 833
        • Recruiting
        • Kaohsiung Chang Gung Memorial Hospital /ID# 267046
  • United Kingdom
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
        • Recruiting
        • Nottingham City Hospital /ID# 266991
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85704
        • Recruiting
        • Arizona Oncology - Tucson - Rudasill /ID# 267552
      • Tucson, Arizona, United States, 85723
        • Recruiting
        • Southern VA Health Care System /ID# 266254
    • California
      • Clovis, California, United States, 93611
        • Recruiting
        • UCSF FRESNO/Community Cancer Institute /ID# 270874
      • Los Angeles, California, United States, 90067
        • Recruiting
        • Valkyrie Clinical Trials /ID# 268151
    • Colorado
      • Aurora, Colorado, United States, 80012
        • Recruiting
        • Rocky Mountain Cancer Centers - Aurora /ID# 267549
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale University School of Medicine /ID# 266224
    • Florida
      • Gainesville, Florida, United States, 32608
        • Recruiting
        • Malcolm Randall V.A. Medical Center /ID# 267825
      • Jacksonville, Florida, United States, 32256
        • Recruiting
        • Cancer Specialists of North Florida - Jacksonville - AC Skinner Parkway /ID# 266713
      • Orange City, Florida, United States, 32763
        • Recruiting
        • Mid Florida Hematology And Oncology Center /ID# 269159
      • St. Petersburg, Florida, United States, 33709
        • Recruiting
        • Comprehensive Hematology Oncology /ID# 267644
    • Illinois
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Springfield Clinic - First /ID# 270145
    • Indiana
      • Dyer, Indiana, United States, 46311
        • Recruiting
        • Northwest Cancer Center - Dyer Clinic /ID# 268478
    • Iowa
      • Des Moines, Iowa, United States, 50314-3017
        • Recruiting
        • University of Iowa Health Care /ID# 267206
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
        • Completed
        • Willis-Knighton Medical Center /ID# 270569
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Recruiting
        • Center for Cancer and Blood Disorders-American Oncology Partners of Maryland /ID# 266445
      • Silver Spring, Maryland, United States, 20904
        • Recruiting
        • Maryland Oncology Hematology - Silver Spring /ID# 267557
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • Recruiting
        • UMass Memorial Medical Center /ID# 270023
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital /ID# 270973
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Recruiting
        • Saint Lukes Hospital of Kansas City /ID# 267270
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai /ID# 266328
    • North Carolina
      • Charlotte, North Carolina, United States, 28204-2963
        • Recruiting
        • Atrium Health /ID# 267219
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Atrium Health Wake Forest Baptist Medical Center /ID# 273142
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Main Campus /ID# 271292
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74146
        • Recruiting
        • Oklahoma Cancer Specialists and Research Institute /ID# 267643
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Recruiting
        • Willamette Valley Cancer Institute and Research Center /ID# 266326
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Lifespan Cancer Institute - Providence /ID# 266550
    • Texas
      • Austin, Texas, United States, 78705
        • Recruiting
        • Texas Oncology - Austin Midtown /ID# 268152
      • Dallas, Texas, United States, 75235
        • Recruiting
        • University of Texas - Southwestern Medical Center /ID# 266528
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists - Fairfax /ID# 268155
    • Washington
      • Olympia, Washington, United States, 98506
        • Recruiting
        • Vista Oncology - East Olympia /ID# 267337
        • Contact:
          • Site Coordinator
          • Phone Number: 360-413-8880 opt 4
      • Tacoma, Washington, United States, 98405
        • Recruiting
        • Northwest Medical Specialties Tacoma /ID# 266327
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Recruiting
        • West Virginia University School of Medicine /ID# 267645

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of documented, previously untreated, chronic lymphocytic leukemia (CLL) requiring treatment according to the 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria and have a life expectancy of > 6 months.
  • Previously untreated small lymphocytic lymphoma (SLL) meeting the 2018 iwCLL criteria for treatment will also be equally considered as CLL for eligibility, screening, treatment and evaluation.
  • Eastern Cooperative Oncology Group (ECOG) performance status <= 2.
  • Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening, unless cytopenia is due to marrow involvement of CLL as listed in the protocol.
  • Creatinine clearance (CrCl) >= 30 mL/min using the Cockcroft-Gault formula are eligible for inclusion.

Exclusion Criteria:

- Active/uncontrolled infection, no Richter's transformation, no active immune thrombocytopenia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Venetoclax + Obinutuzumab
Participants will receive venetoclax in combination with obinutuzumab, with a 5 week venetoclax ramp up.
Drug: Obinutuzumab
Intravenous Infusion
Drug: Venetoclax
Oral: Tablet
Other Names:
  • ABT-199
Experimental: Arm B: Venetoclax + Acalabrutinib
Participants will receive venetoclax in combination with acalabrutinib, with a 5 week venetoclax ramp up.
Drug: Venetoclax
Oral: Tablet
Other Names:
  • ABT-199
Drug: Acalabrutinib
Oral: Tablet
Experimental: Arm C: Venetoclax + Acalabrutinib
Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up A.
Drug: Venetoclax
Oral: Tablet
Other Names:
  • ABT-199
Drug: Acalabrutinib
Oral: Tablet
Experimental: Arm D: Venetoclax + Acalabrutinib
Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up B.
Drug: Venetoclax
Oral: Tablet
Other Names:
  • ABT-199
Drug: Acalabrutinib
Oral: Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Percentage of Participants with Treatment-Emergent Laboratory Tumor Lysis Syndrome (TLS)-Venetoclax
Time Frame: Up to 28 Months
TLS is defined per Howard criteria that require a clinical intervention per independent review committee (IRC) assessment during the venetoclax ramp-up period in previously untreated participants with chronic lymphocytic leukemia (CLL) achieving a medium tumor burden with creatinine clearance (CrCl) of at least 80 ml/min or low tumor burden (regardless of CrCl level) after debulking therapy.
Up to 28 Months
Part 1: Percentage of Participants with Hyperkalemia-Venetoclax
Time Frame: Up to 28 Months
Hyperkalemia (potassium >6.0 mmol/L) is defined per Howard criteria that require a clinical intervention per IRC assessment during the venetoclax ramp-up period in previously untreated participants with CLL achieving a medium tumor burden with CrCl of at least 80 ml/min or low tumor burden (regardless of CrCl level) after debulking therapy.
Up to 28 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Percentage of Participants with Treatment-Emergent Laboratory TLS
Time Frame: Up to 28 Months
TLS is defined per Howard criteria that require a clinical intervention per IRC assessment, at each dose level and at each laboratory monitoring point during ramp-up period in previously untreated participants with CLL achieving a medium tumor burden with CrCl of at least 80 ml/min or low tumor burden (regardless of CrCl level) after debulking therapy.
Up to 28 Months
Part 1: Percentage of Participants with Hyperkalemia
Time Frame: Up to 28 Months
Hyperkalemia (potassium >6.0 mmol/L) is defined per Howard criteria that require a clinical intervention per independent review committee (IRC) assessment during the venetoclax ramp-up period in previously untreated participants with CLL achieving a medium tumor burden with CrCl of at least 80 ml/min or low tumor burden (regardless of CrCl level) after debulking therapy.
Up to 28 Months
Part 1: Percentage of Participants with Adverse Events (AE) of TLS
Time Frame: Up to 28 Months
AEs of TLS is defined as a blood chemistry changes or symptom suggestive of TLS.
Up to 28 Months
Part 1: Percentage of Participants with Reduction of Tumor Burden from Baseline
Time Frame: Up to 28 Months
Percentage of participants with reduction of tumor burden.
Up to 28 Months
Part 1: Percentage of Participants with Treatment-Emergent TLS-Related Events
Time Frame: Up to 28 Months
TLS-related events are defined as laboratory TLS per Howard criteria requiring clinical intervention per IRC assessment, hyperkalemia (potassium >6.0 mmol/L) requiring clinical intervention per IRC assessment, laboratory TLS per Howard criteria irrespective of clinical intervention, Hyperkalemia (potassium >6.0 mmol/L) irrespective of clinical intervention, clinical TLS per Howard criteria irrespective of clinical intervention, any single TLS-related lab abnormality requiring clinical intervention per Investigator.
Up to 28 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie

Investigators

  • Study Director: ABBVIE INC., AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 5, 2024

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2028

Study Registration Dates

First Submitted

May 20, 2024

First Submitted That Met QC Criteria

May 20, 2024

First Posted (Actual)

May 24, 2024

Study Record Updates

Last Update Posted (Actual)

April 9, 2026

Last Update Submitted That Met QC Criteria

April 6, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M24-287
  • 2024-512147-23-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.

IPD Sharing Time Frame

For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

IPD Sharing Access Criteria

To learn more about 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

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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