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
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.
Arms & interventions
- DrugVenetoclax
Oral: Tablet
- DrugAcalabrutinib
Oral: Tablet
- DrugObinutuzumab
Intravenous Infusion
Outcome measures
Primary
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.
Time frame: 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.
Time frame: Up to 28 Months
Secondary
Part 1: Percentage of Participants with Treatment-Emergent Laboratory TLS
Time frame: Up to 28 Months
Part 1: Percentage of Participants with Hyperkalemia
Time frame: Up to 28 Months
Part 1: Percentage of Participants with Treatment-Emergent TLS-Related Events
Time frame: Up to 28 Months
Part 1: Percentage of Participants with Adverse Events (AE) of TLS
Time frame: Up to 28 Months
Part 1: Percentage of Participants with Reduction of Tumor Burden from Baseline
Time frame: Up to 28 Months
Eligibility criteria
Study locations (32)
Arizona Oncology - Tucson - Rudasill /ID# 267552
Tucson, Arizona, 85704
Southern VA Health Care System /ID# 266254
Tucson, Arizona, 85723
UCSF FRESNO/Community Cancer Institute /ID# 270874
Clovis, California, 93611
Valkyrie Clinical Trials /ID# 268151
Los Angeles, California, 90067
Rocky Mountain Cancer Centers - Aurora /ID# 267549
Aurora, Colorado, 80012
Yale University School of Medicine /ID# 266224
New Haven, Connecticut, 06510
Malcolm Randall V.A. Medical Center /ID# 267825
Gainesville, Florida, 32608
Cancer Specialists of North Florida - Jacksonville - AC Skinner Parkway /ID# 266713
Jacksonville, Florida, 32256
Mid Florida Hematology And Oncology Center /ID# 269159
Orange City, Florida, 32763
Comprehensive Hematology Oncology /ID# 267644
St. Petersburg, Florida, 33709
Springfield Clinic - First /ID# 270145
Springfield, Illinois, 62702
Northwest Cancer Center - Dyer Clinic /ID# 268478
Dyer, Indiana, 46311
University of Iowa Health Care /ID# 267206
Des Moines, Iowa, 50314-3017
Willis-Knighton Medical Center /ID# 270569
Shreveport, Louisiana, 71103
Center for Cancer and Blood Disorders-American Oncology Partners of Maryland /ID# 266445
Bethesda, Maryland, 20817
Maryland Oncology Hematology - Silver Spring /ID# 267557
Silver Spring, Maryland, 20904
UMass Memorial Medical Center /ID# 270023
Worcester, Massachusetts, 01655
Henry Ford Hospital /ID# 270973
Detroit, Michigan, 48202
Saint Lukes Hospital of Kansas City /ID# 267270
Kansas City, Missouri, 64111
Icahn School of Medicine at Mount Sinai /ID# 266328
New York, New York, 10029
Atrium Health /ID# 267219
Charlotte, North Carolina, 28204-2963
Atrium Health Wake Forest Baptist Medical Center /ID# 273142
Winston-Salem, North Carolina, 27157
Cleveland Clinic Main Campus /ID# 271292
Cleveland, Ohio, 44195
Oklahoma Cancer Specialists and Research Institute /ID# 267643
Tulsa, Oklahoma, 74146
Willamette Valley Cancer Institute and Research Center /ID# 266326
Eugene, Oregon, 97401
Lifespan Cancer Institute - Providence /ID# 266550
Providence, Rhode Island, 02903
Texas Oncology - Austin Midtown /ID# 268152
Austin, Texas, 78705
University of Texas - Southwestern Medical Center /ID# 266528
Dallas, Texas, 75235
Virginia Cancer Specialists - Fairfax /ID# 268155
Fairfax, Virginia, 22031
Vista Oncology - East Olympia /ID# 267337
Olympia, Washington, 98506
Northwest Medical Specialties Tacoma /ID# 266327
Tacoma, Washington, 98405
West Virginia University School of Medicine /ID# 267645
Morgantown, West Virginia, 26506