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)
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT06428019
- Lead Sponsor
- AbbVie
- 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 120 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- 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.
- Active/uncontrolled infection, no Richter's transformation, no active immune thrombocytopenia.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm D: Venetoclax + Acalabrutinib Acalabrutinib Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up B. Arm D: Venetoclax + Acalabrutinib Venetoclax Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up B. Arm A: Venetoclax + Obinutuzumab Obinutuzumab Participants will receive venetoclax in combination with obinutuzumab, with a 5 week venetoclax ramp up. Arm A: Venetoclax + Obinutuzumab Venetoclax Participants will receive venetoclax in combination with obinutuzumab, with a 5 week venetoclax ramp up. Arm B: Venetoclax + Acalabrutinib Venetoclax Participants will receive venetoclax in combination with acalabrutinib, with a 5 week venetoclax ramp up. Arm B: Venetoclax + Acalabrutinib Acalabrutinib Participants will receive venetoclax in combination with acalabrutinib, with a 5 week venetoclax ramp up. Arm C: Venetoclax + Acalabrutinib Venetoclax Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up A. Arm C: Venetoclax + Acalabrutinib Acalabrutinib Participants will receive venetoclax in combination with acalabrutinib, with a modified venetoclax ramp up A.
- Primary Outcome Measures
Name Time Method Part 1: Percentage of Participants with Treatment-Emergent Laboratory Tumor Lysis Syndrome (TLS)-Venetoclax 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.
Part 1: Percentage of Participants with Hyperkalemia-Venetoclax 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.
- Secondary Outcome Measures
Name Time Method Part 1: Percentage of Participants with Treatment-Emergent Laboratory TLS 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.
Part 1: Percentage of Participants with Hyperkalemia 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.
Part 1: Percentage of Participants with Treatment-Emergent TLS-Related Events 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.
Part 1: Percentage of Participants with Adverse Events (AE) of TLS Up to 28 Months AEs of TLS is defined as a blood chemistry changes or symptom suggestive of TLS.
Part 1: Percentage of Participants with Reduction of Tumor Burden from Baseline Up to 28 Months Percentage of participants with reduction of tumor burden.
Trial Locations
- Locations (64)
West Virginia University School of Medicine /ID# 267645
🇺🇸Morgantown, West Virginia, United States
Arizona Oncology - Tucson - Rudasill /ID# 267552
🇺🇸Tucson, Arizona, United States
UCSF FRESNO/Community Cancer Institute /ID# 270874
🇺🇸Clovis, California, United States
Valkyrie Clinical Trials /ID# 268151
🇺🇸Los Angeles, California, United States
Rocky Mountain Cancer Centers - Aurora /ID# 267549
🇺🇸Aurora, Colorado, United States
Yale University School of Medicine /ID# 266224
🇺🇸New Haven, Connecticut, United States
Malcolm Randall V.A. Medical Center /ID# 267825
🇺🇸Gainesville, Florida, United States
Cancer Specialists of North Florida - Jacksonville - AC Skinner Parkway /ID# 266713
🇺🇸Jacksonville, Florida, United States
Mid Florida Hematology And Oncology Center /ID# 269159
🇺🇸Orange City, Florida, United States
Comprehensive Hematology Oncology /ID# 267644
🇺🇸Saint Petersburg, Florida, United States
Springfield Clinic /ID# 270145
🇺🇸Springfield, Illinois, United States
Northwest Cancer Center - Dyer Clinic /ID# 268478
🇺🇸Dyer, Indiana, United States
University of Iowa Health Care /ID# 267206
🇺🇸Des Moines, Iowa, United States
Willis-Knighton Medical Center /ID# 270569
🇺🇸Shreveport, Louisiana, United States
American Oncology Partners of Maryland /ID# 266445
🇺🇸Bethesda, Maryland, United States
Maryland Oncology Hematology - Silver Spring /ID# 267557
🇺🇸Silver Spring, Maryland, United States
Saint Luke's Hospital of Kansas City /ID# 267270
🇺🇸Kansas City, Missouri, United States
Cleveland Clinic Main Campus /ID# 271292
🇺🇸Cleveland, Ohio, United States
Oklahoma Cancer Specialists and Research Institute /ID# 267643
🇺🇸Tulsa, Oklahoma, United States
Willamette Valley Cancer Institute and Research Center /ID# 266326
🇺🇸Eugene, Oregon, United States
Lifespan Cancer Institute - Providence /ID# 266550
🇺🇸Providence, Rhode Island, United States
Texas Oncology - Austin Midtown /ID# 268152
🇺🇸Austin, Texas, United States
University of Texas - Southwestern Medical Center /ID# 266528
🇺🇸Dallas, Texas, United States
Virginia Cancer Specialists - Gainesville /ID# 268155
🇺🇸Gainesville, Virginia, United States
Vista Oncology - East Olympia /ID# 267337
🇺🇸Olympia, Washington, United States
Northwest Medical Specialties Tacoma /ID# 266327
🇺🇸Tacoma, Washington, United States
Calvary Mater Newcastle /ID# 267408
🇦🇺Waratah, New South Wales, Australia
Townsville University Hospital /ID# 266954
🇦🇺Townsville, Queensland, Australia
St Vincent's Hospital - Melbourne /ID# 270027
🇦🇺Fitzroy, Victoria, Australia
Royal Perth Hospital /ID# 266906
🇦🇺Perth, Western Australia, Australia
Centre Hospitalier Universitaire de Saint Etienne - Hopital Nord /ID# 266319
🇫🇷St-Priest-en-Jarez, Loire, France
CHR Metz-Thionville - Hôpital de Mercy /ID# 266852
🇫🇷Ars Laquenexy, Moselle, France
Hopitaux Universitaires Henri Mondor - Hopital Henri Mondor /ID# 266270
🇫🇷Creteil, Paris, France
Hopitaux Universitaires Paris Centre-Hopital Cochin /ID# 267438
🇫🇷Paris CEDEX 14, Paris, France
Centre Antoine-Lacassagne /ID# 266894
🇫🇷Nice, Provence-Alpes-Cote-d Azur, France
Centre Hospitalier de la Côte Basque /ID# 266847
🇫🇷Bayonne, Pyrenees-Atlantiques, France
Centre Hospitalier Métropole Savoie - Site Hôpital de Chambéry /ID# 266854
🇫🇷Chambery CEDEX, Savoie, France
CHU d'Amiens-Picardie - Hôpital Sud /ID# 266849
🇫🇷Amiens CEDEX 1, Somme, France
Centre Hospitalier d'Argenteuil Victor Dupouy /ID# 266322
🇫🇷Argenteuil, France
Centre Hospitalier Régional d'Orléans - Hôpital de la Source /ID# 266272
🇫🇷Orléans, France
Olympion General Clinic /ID# 266819
🇬🇷Patras, Achaia, Greece
Evangelismos Hospital /ID# 266815
🇬🇷Athens, Attiki, Greece
General Hospital of Athens Laiko /ID# 266813
🇬🇷Athens, Attiki, Greece
University General Hospital Attikon /ID# 266814
🇬🇷Athens, Attiki, Greece
University General Hospital of Alexandroupoli /ID# 266816
🇬🇷Alexandroupoli, Evros, Greece
Pan American Center for Oncology Trials /ID# 266243
🇵🇷Rio Piedras, Puerto Rico
Clinical Hospital Center Zvezdara /ID# 266560
🇷🇸Belgrade, Beograd, Serbia
University Clinical Center Serbia /ID# 266579
🇷🇸Belgrade, Beograd, Serbia
Clinical Hospital Center - Bežanijska Kosa /ID# 266567
🇷🇸Belgrade, Beograd, Serbia
University Clinical Center Nis /ID# 266580
🇷🇸Niš, Nisavski Okrug, Serbia
University Clinical Center Kragujevac /ID# 266568
🇷🇸Kragujevac, Sumadijski Okrug, Serbia
Institute for Oncology of Vojvodina /ID# 266556
🇷🇸Sremska Kamenica, Vojvodina, Serbia
University Clinical Center Vojvodina /ID# 266674
🇷🇸Novi Sad, Serbia
Complejo Hospitalario Universitario de Santiago (CHUS) /ID# 267164
🇪🇸Santiago de Compostela, A Coruna, Spain
Hospital Universitario Puerta de Hierro - Majadahonda /ID# 266967
🇪🇸Majadahonda, Madrid, Spain
Clinica Universidad de Navarra - Pamplona /ID# 267762
🇪🇸Pamplona, Navarra, Spain
CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 266969
🇪🇸Madrid, Spain
Hospital MD Anderson Cancer Center Madrid /ID# 267167
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio /ID# 266968
🇪🇸Sevilla, Spain
Kaohsiung Chang Gung Memorial Hospital /ID# 267046
🇨🇳Kaohsiung City, Kaohsiung, Taiwan
National Taiwan University Hospital /ID# 267017
🇨🇳Taipei City, Taipei, Taiwan
China Medical University Hospital /ID# 267018
🇨🇳Taichung, Taiwan
Linkou Chang Gung Memorial Hospital /ID# 267045
🇨🇳Taoyuan City, Taiwan
Nottingham City Hospital /ID# 266991
🇬🇧Nottingham, Nottinghamshire, United Kingdom