Clinical trial NCT06428019: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia
CLL
Venetoclax
ABT-199
Obinutuzumab
Acalabrutinib
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-05-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Percentage of Participants with Treatment-Emergent Laboratory Tumor Lysis Syndrome (TLS)-Venetoclax
timeFrame: Up to 28 Months
measure: Part 1: Percentage of Participants with Hyperkalemia-Venetoclax
timeFrame: Up to 28 Months
Secondary outcomes:
measure: Part 1: Percentage of Participants with Treatment-Emergent Laboratory TLS
timeFrame: Up to 28 Months
measure: Part 1: Percentage of Participants with Hyperkalemia
timeFrame: Up to 28 Months
measure: Part 1: Percentage of Participants with Treatment-Emergent TLS-Related Events
timeFrame: Up to 28 Months
measure: Part 1: Percentage of Participants with Adverse Events (AE) of TLS
timeFrame: Up to 28 Months
measure: Part 1: Percentage of Participants with Reduction of Tumor Burden from Baseline
timeFrame: Up to 28 Months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology - Tucson - Rudasill /ID# 267552
state: Arizona
city: Clovis
country: United States
facility: UCSF FRESNO/Community Cancer Institute /ID# 270874
state: California
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials /ID# 268151
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora /ID# 267549
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine /ID# 266224
state: Connecticut
city: Gainesville
country: United States
facility: Malcolm Randall V.A. Medical Center /ID# 267825
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida - Jacksonville - AC Skinner Parkway /ID# 266713
state: Florida
city: Orange City
country: United States
facility: Mid Florida Hematology And Oncology Center /ID# 269159
state: Florida
city: Saint Petersburg
country: United States
facility: Comprehensive Hematology Oncology /ID# 267644
state: Florida
city: Springfield
country: United States
facility: Springfield Clinic /ID# 270145
state: Illinois
city: Dyer
country: United States
facility: Northwest Cancer Center - Dyer Clinic /ID# 268478
state: Indiana
city: Des Moines
country: United States
facility: University of Iowa Health Care /ID# 267206
state: Iowa
city: Shreveport
country: United States
facility: Willis-Knighton Medical Center /ID# 270569
state: Louisiana
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland /ID# 266445
state: Maryland
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology - Silver Spring /ID# 267557
state: Maryland
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City /ID# 267270
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus /ID# 271292
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute /ID# 267643
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center /ID# 266326
state: Oregon
city: Providence
country: United States
facility: Lifespan Cancer Institute - Providence /ID# 266550
state: Rhode Island
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown /ID# 268152
state: Texas
city: Dallas
country: United States
facility: University of Texas - Southwestern Medical Center /ID# 266528
state: Texas
city: Gainesville
country: United States
facility: Virginia Cancer Specialists - Gainesville /ID# 268155
state: Virginia
city: Olympia
country: United States
facility: Vista Oncology - East Olympia /ID# 267337
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties Tacoma /ID# 266327
state: Washington
city: Morgantown
country: United States
facility: West Virginia University School of Medicine /ID# 267645
state: West Virginia
city: Waratah
country: Australia
facility: Calvary Mater Newcastle /ID# 267408
state: New South Wales
city: Townsville
country: Australia
facility: Townsville University Hospital /ID# 266954
state: Queensland
city: Fitzroy
country: Australia
facility: St Vincent's Hospital - Melbourne /ID# 270027
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital /ID# 266906
state: Western Australia
city: St-Priest-en-Jarez
country: France
facility: Centre Hospitalier Universitaire de Saint Etienne - Hopital Nord /ID# 266319
state: Loire
city: Ars Laquenexy
country: France
facility: CHR Metz-Thionville - Hôpital de Mercy /ID# 266852
state: Moselle
city: Creteil
country: France
facility: Hopitaux Universitaires Henri Mondor - Hopital Henri Mondor /ID# 266270
state: Paris
city: Paris CEDEX 14
country: France
facility: Hopitaux Universitaires Paris Centre-Hopital Cochin /ID# 267438
state: Paris
city: Nice
country: France
facility: Centre Antoine-Lacassagne /ID# 266894
state: Provence-Alpes-Cote-d Azur
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque /ID# 266847
state: Pyrenees-Atlantiques
city: Chambery CEDEX
country: France
facility: Centre Hospitalier Métropole Savoie - Site Hôpital de Chambéry /ID# 266854
state: Savoie
city: Amiens CEDEX 1
country: France
facility: CHU d'Amiens-Picardie - Hôpital Sud /ID# 266849
state: Somme
city: Argenteuil
country: France
facility: Centre Hospitalier d'Argenteuil Victor Dupouy /ID# 266322
city: Orléans
country: France
facility: Centre Hospitalier Régional d'Orléans - Hôpital de la Source /ID# 266272
city: Patras
country: Greece
facility: Olympion General Clinic /ID# 266819
state: Achaia
city: Athens
country: Greece
facility: Evangelismos Hospital /ID# 266815
state: Attiki
city: Athens
country: Greece
facility: General Hospital of Athens Laiko /ID# 266813
state: Attiki
city: Athens
country: Greece
facility: University General Hospital Attikon /ID# 266814
state: Attiki
city: Alexandroupoli
country: Greece
facility: University General Hospital of Alexandroupoli /ID# 266816
state: Evros
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials /ID# 266243
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zvezdara /ID# 266560
state: Beograd
city: Belgrade
country: Serbia
facility: University Clinical Center Serbia /ID# 266579
state: Beograd
city: Belgrade
country: Serbia
facility: Clinical Hospital Center - Bežanijska Kosa /ID# 266567
state: Beograd
city: Niš
country: Serbia
facility: University Clinical Center Nis /ID# 266580
state: Nisavski Okrug
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac /ID# 266568
state: Sumadijski Okrug
city: Sremska Kamenica
country: Serbia
facility: Institute for Oncology of Vojvodina /ID# 266556
state: Vojvodina
city: Novi Sad
country: Serbia
facility: University Clinical Center Vojvodina /ID# 266674
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) /ID# 267164
state: A Coruna
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda /ID# 266967
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona /ID# 267762
state: Navarra
city: Madrid
country: Spain
facility: CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 266969
city: Madrid
country: Spain
facility: Hospital MD Anderson Cancer Center Madrid /ID# 267167
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 266968
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital /ID# 267046
state: Kaohsiung
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 267017
state: Taipei
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 267018
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 267045
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital /ID# 266991
state: Nottinghamshire
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: