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)

NCT06428019 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: M24-2872024-512147-23-00
• Study Type: interventional
• Target: 170
• Locations: 9 countries
• Sites: 70

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia; CLL; Venetoclax; ABT-199; Obinutuzumab; Acalabrutinib

Outcome Measures

Primary Outcomes (2)

• Part 1: Percentage of Participants with Treatment-Emergent Laboratory Tumor Lysis Syndrome (TLS)-Venetoclax

  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

  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 Outcomes (5)

• Part 1: Percentage of Participants with Treatment-Emergent Laboratory TLS

  Up to 28 Months

• Part 1: Percentage of Participants with Hyperkalemia

  Up to 28 Months

• Part 1: Percentage of Participants with Treatment-Emergent TLS-Related Events

  Up to 28 Months

• Part 1: Percentage of Participants with Adverse Events (AE) of TLS

  Up to 28 Months

• Part 1: Percentage of Participants with Reduction of Tumor Burden from Baseline

  Up to 28 Months

Study Arms (4)

Arm A: Venetoclax + Obinutuzumab

EXPERIMENTAL

Participants will receive venetoclax in combination with obinutuzumab, with a 5 week venetoclax ramp up.

Drug: Venetoclax; Drug: Obinutuzumab

Arm B: Venetoclax + Acalabrutinib

EXPERIMENTAL

Participants will receive venetoclax in combination with acalabrutinib, with a 5 week venetoclax ramp up.

Drug: Venetoclax; Drug: Acalabrutinib

Arm C: Venetoclax + Acalabrutinib

EXPERIMENTAL

Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up A.

Drug: Venetoclax; Drug: Acalabrutinib

Arm D: Venetoclax + Acalabrutinib

EXPERIMENTAL

Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up B.

Drug: Venetoclax; Drug: Acalabrutinib

Interventions

Venetoclax DRUG

Oral: Tablet

Also known as: ABT-199

Arm A: Venetoclax + Obinutuzumab; Arm B: Venetoclax + Acalabrutinib; Arm C: Venetoclax + Acalabrutinib; Arm D: Venetoclax + Acalabrutinib

Acalabrutinib DRUG

Oral: Tablet

Arm B: Venetoclax + Acalabrutinib; Arm C: Venetoclax + Acalabrutinib; Arm D: Venetoclax + Acalabrutinib

Obinutuzumab DRUG

Intravenous Infusion

Arm A: Venetoclax + Obinutuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (70)

Arizona Oncology - Tucson - Rudasill /ID# 267552

Tucson, Arizona, 85704, United States

RECRUITING

Southern VA Health Care System /ID# 266254

Tucson, Arizona, 85723, United States

RECRUITING

UCSF FRESNO/Community Cancer Institute /ID# 270874

Clovis, California, 93611, United States

RECRUITING

Valkyrie Clinical Trials /ID# 268151

Los Angeles, California, 90067, United States

RECRUITING

Rocky Mountain Cancer Centers - Aurora /ID# 267549

Aurora, Colorado, 80012, United States

RECRUITING

Yale University School of Medicine /ID# 266224

New Haven, Connecticut, 06510, United States

RECRUITING

Malcolm Randall V.A. Medical Center /ID# 267825

Gainesville, Florida, 32608, United States

RECRUITING

Cancer Specialists of North Florida - Jacksonville - AC Skinner Parkway /ID# 266713

Jacksonville, Florida, 32256, United States

RECRUITING

Mid Florida Hematology And Oncology Center /ID# 269159

Orange City, Florida, 32763, United States

RECRUITING

Comprehensive Hematology Oncology /ID# 267644

St. Petersburg, Florida, 33709, United States

RECRUITING

Springfield Clinic - First /ID# 270145

Springfield, Illinois, 62702, United States

RECRUITING

Northwest Cancer Center - Dyer Clinic /ID# 268478

Dyer, Indiana, 46311, United States

RECRUITING

University of Iowa Health Care /ID# 267206

Des Moines, Iowa, 50314-3017, United States

RECRUITING

Willis-Knighton Medical Center /ID# 270569

Shreveport, Louisiana, 71103, United States

COMPLETED

Center for Cancer and Blood Disorders-American Oncology Partners of Maryland /ID# 266445

Bethesda, Maryland, 20817, United States

RECRUITING

Maryland Oncology Hematology - Silver Spring /ID# 267557

Silver Spring, Maryland, 20904, United States

RECRUITING

UMass Memorial Medical Center /ID# 270023

Worcester, Massachusetts, 01655, United States

RECRUITING

Henry Ford Hospital /ID# 270973

Detroit, Michigan, 48202, United States

RECRUITING

Saint Lukes Hospital of Kansas City /ID# 267270

Kansas City, Missouri, 64111, United States

RECRUITING

Icahn School of Medicine at Mount Sinai /ID# 266328

New York, New York, 10029, United States

RECRUITING

Atrium Health /ID# 267219

Charlotte, North Carolina, 28204-2963, United States

RECRUITING

Atrium Health Wake Forest Baptist Medical Center /ID# 273142

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Cleveland Clinic Main Campus /ID# 271292

Cleveland, Ohio, 44195, United States

RECRUITING

Oklahoma Cancer Specialists and Research Institute /ID# 267643

Tulsa, Oklahoma, 74146, United States

RECRUITING

Willamette Valley Cancer Institute and Research Center /ID# 266326

Eugene, Oregon, 97401, United States

RECRUITING

Lifespan Cancer Institute - Providence /ID# 266550

Providence, Rhode Island, 02903, United States

RECRUITING

Texas Oncology - Austin Midtown /ID# 268152

Austin, Texas, 78705, United States

RECRUITING

University of Texas - Southwestern Medical Center /ID# 266528

Dallas, Texas, 75235, United States

RECRUITING

Virginia Cancer Specialists - Fairfax /ID# 268155

Fairfax, Virginia, 22031, United States

RECRUITING

Vista Oncology - East Olympia /ID# 267337

Olympia, Washington, 98506, United States

RECRUITING

Northwest Medical Specialties Tacoma /ID# 266327

Tacoma, Washington, 98405, United States

RECRUITING

West Virginia University School of Medicine /ID# 267645

Morgantown, West Virginia, 26506, United States

RECRUITING

Calvary Mater Newcastle /ID# 267408

Waratah, New South Wales, 2298, Australia

RECRUITING

Townsville University Hospital /ID# 266954

Townsville, Queensland, 4814, Australia

RECRUITING

St Vincent's Hospital - Melbourne /ID# 270027

Fitzroy, Victoria, 3065, Australia

RECRUITING

Royal Perth Hospital /ID# 266906

Perth, Western Australia, 6000, Australia

RECRUITING

Centre Hospitalier Régional Metz Thionville - Hôpital de Mercy /ID# 266852

Metz, Moselle, 57085, France

RECRUITING

Hopitaux Universitaires Henri Mondor - Hopital Henri Mondor /ID# 266270

Créteil, Paris, 94010, France

RECRUITING

Hopitaux Universitaires Paris Centre-Hopital Cochin /ID# 267438

Paris, Paris, 75679, France

RECRUITING

Centre Hospitalier Universitaire de Saint Etienne - Hopital Nord /ID# 266319

St-Priest-en-Jarez, Pays de la Loire Region, 42270, France

RECRUITING

Centre Antoine-Lacassagne /ID# 266894

Nice, Provence-Alpes-Côte d'Azur Region, 06189, France

RECRUITING

Centre Hospitalier de la Côte Basque /ID# 266847

Bayonne, Pyrenees-Atlantiques, 64109, France

RECRUITING

Centre Hospitalier Métropole Savoie - Site Hôpital de Chambéry /ID# 266854

Chambéry, Savoie, 73007, France

RECRUITING

CHU Amiens-Picardie Site Sud /ID# 266849

Amiens, Somme, 80054, France

RECRUITING

Centre Hospitalier Régional d'Orléans - Hôpital de la Source /ID# 266272

Orléans, 45067, France

RECRUITING

Centre Hospitalier d Argenteuil Victor Dupouy /ID# 266322

Argenteuil, Île-de-France Region, 95107, France

RECRUITING

Olympion General Clinic /ID# 266819

Pátrai, Achaia, 26443, Greece

RECRUITING

Evangelismos Hospital /ID# 266815

Athens, Attica, 10676, Greece

RECRUITING

General Hospital of Athens Laiko /ID# 266813

Athens, Attica, 11527, Greece

RECRUITING

University General Hospital Attikon /ID# 266814

Athens, Attica, 12462, Greece

RECRUITING

University General Hospital of Alexandroupoli /ID# 266816

Alexandroupoli, Evros, 68100, Greece

RECRUITING

Pan American Center for Oncology Trials /ID# 266243

Rio Piedras, 00935, Puerto Rico

RECRUITING

Clinical Hospital Center Zvezdara /ID# 266560

Belgrade, Beograd, 11000, Serbia

RECRUITING

University Clinical Center Serbia /ID# 266579

Belgrade, Beograd, 11000, Serbia

RECRUITING

Clinical Hospital Center - Bežanijska Kosa /ID# 266567

Belgrade, Beograd, 11080, Serbia

RECRUITING

University Clinical Center Nis /ID# 266580

Niš, Nisavski Okrug, 18300, Serbia

RECRUITING

University Clinical Center Kragujevac /ID# 266568

Kragujevac, Sumadijski Okrug, 34000, Serbia

RECRUITING

Institute for Oncology of Vojvodina /ID# 266556

Kamenitz, Vojvodina, 21208, Serbia

RECRUITING

University Clinical Center Vojvodina /ID# 266674

Novi Sad, 21000, Serbia

RECRUITING

Complejo Hospitalario Universitario de Santiago (CHUS) /ID# 267164

Santiago de Compostela, A Coruna, 15706, Spain

RECRUITING

Hospital Universitario Puerta de Hierro - Majadahonda /ID# 266967

Majadahonda, Madrid, 28222, Spain

RECRUITING

Clinica Universidad de Navarra - Pamplona /ID# 267762

Pamplona, Navarre, 31008, Spain

RECRUITING

CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 266969

Madrid, 28027, Spain

RECRUITING

Hospital MD Anderson Cancer Center Madrid /ID# 267167

Madrid, 28033, Spain

RECRUITING

Hospital Universitario Virgen del Rocio /ID# 266968

Seville, 41013, Spain

RECRUITING

Kaohsiung Chang Gung Memorial Hospital /ID# 267046

Kaohsiung City, Kaohsiung, 833, Taiwan

RECRUITING

China Medical University Hospital /ID# 267018

Taichung, 40447, Taiwan

RECRUITING

National Taiwan University Hospital /ID# 267017

Taipei, 100, Taiwan

RECRUITING

Linkou Chang Gung Memorial Hospital /ID# 267045

Taoyuan, 333, Taiwan

RECRUITING

Nottingham City Hospital /ID# 266991

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

venetoclax; acalabrutinib; obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Central Study Contacts

ABBVIE CALL CENTER

CONTACT

844-663-3742; abbvieclinicaltrials@abbvie.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2024
• First Posted: May 24, 2024
• Study Start: August 5, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

Locations

FR (10); PR (1); US (32); GR (5); GB (1); AU (4); ES (6); SE (7); TW (4)