Testing sonrotoclax added to zanubrutinib for untreated chronic lymphocytic leukemia
Tests adding sonrotoclax to zanubrutinib in older adults with untreated CLL.
Plain-language title generated from the registry record
Registry title: Testing the Addition of Anti-Cancer Drug Sonrotoclax, to the Standard Treatment Zanubrutinib, for Previously Untreated CLL/SLL
Key facts
- Where
- Aberdeen, Abilene, Akron, Ames, Anaconda, Anaheim, Ankeny, Ashland, Athens, Avon, Baker City, Baldwin Park, Bellflower, Bemidji, Billings, Birmingham, Bismarck, Bloomington, Boise, Boston, Bozeman, Brainerd, Brighton, Burnsville, Caldwell, Canton, Cape Girardeau, Carroll, Carthage, Cedar Rapids, Chanute, Chapel Hill, Chelsea, Cherry Hill, Chicago, City of Saint Peters, Cleveland, Clive, Coeur d'Alene, Collierville, Colorado Springs, Columbus, Coon Rapids, Coral Gables, Coral Springs, Creve Coeur, Danville, Decatur, Deer River, Deerfield Beach, Delaware, Denver, Des Moines, Detroit, Dixon, Dodge City, Doral, Dublin, Duluth, Durham, Edina, Edmonds, Effingham, El Dorado, Eureka, Fargo, Farmington, Farmington Hills, Fontana, Fort Dodge, Fremont, Fresno, Galesburg, Glens Falls, Grand Junction, Great Falls, Green Bay, Harbor City, Hays, Hendersonville, Hibbing, Hollywood, Honolulu, Independence, Irvine, Issaquah, Jersey City, Jupiter, Kalispell, Kansas City, Kewanee, Kingman, La Crosse, Lafayette, Lakeland, Lansing, Lawrence, Lee's Summit, Liberal, Livingston, Livonia, Lone Tree, Long Branch, Los Angeles, Louisville, Macomb, Madison, Mansfield, Marion, Marshalltown, Mattoon, Mayfield Heights, McPherson, Memphis, Meridian, Miami, Miami Beach, Minneapolis, Missoula, Mitchell, Modesto, Monroe, Mukwonago, Nampa, New Brunswick, New York, Newark, Newberg, Newton, Normal, North Miami, O'Fallon, Oakland, Oconomowoc, Oconto Falls, Oklahoma City, Olathe, Ontario, Oregon City, Ottawa, Overland Park, Panorama City, Parsons, Pekin, Pella, Peoria, Peru, Philadelphia, Pickerington, Pierre, Plantation, Pontiac, Portland, Post Falls, Pratt, Princeton, Providence, Richmond, Riverside, Rochester, Rockford, Roseville, Sacramento, Saint Louis Park, Saint Paul, Sainte Genevieve, Salina, San Diego, San Francisco, San Jose, San Leandro, San Marcos, San Rafael, Sandpoint, Sandstone, Santa Clara, Santa Rosa, Seattle, Sewell, Shiloh, Shreveport, Sioux Falls, South Portland, South San Francisco, Southhaven, Springfield, St Louis, Sturgeon Bay, Sullivan, Tappahannock, Topeka, Urbana, Vallejo, Virginia, Walnut Creek, Washington, Waukee, Waukesha, Webster, Wellington, Westerville, Westwood, Wichita, Wilkes-Barre, Winfield, Woodbury, Woodland Hills, Yankton, and Ypsilanti, United StatesSee the 261 sites
- Phase
- Phase 3
Where in United States
- Avera Cancer Institute-AberdeenAberdeen, United StatesTaking people
- Hendrick Medical CenterAbilene, United StatesTaking people
- Cleveland Clinic Akron GeneralAkron, United StatesTaking people
- Mary Greeley Medical CenterAmes, United StatesTaking people
- McFarland Clinic - AmesAmes, United StatesTaking people
- Community Hospital of AnacondaAnaconda, United StatesTaking people
- Kaiser Permanente-AnaheimAnaheim, United StatesTaking people
- UI Health Care Mission Cancer and Blood - Ankeny ClinicAnkeny, United StatesTaking people
- Duluth Clinic AshlandAshland, United StatesTaking people
- OhioHealth O'Bleness HospitalAthens, United StatesTaking people
- Avon - Richard E Jacobs Health CenterAvon, United StatesTaking people
- Saint Alphonsus Cancer Care Center-Baker CityBaker City, United StatesTaking people
- Kaiser Permanente-Baldwin ParkBaldwin Park, United StatesTaking people
- Kaiser Permanente-BellflowerBellflower, United StatesTaking people
- Sanford Joe Lueken Cancer CenterBemidji, United StatesTaking people
- Billings Clinic Cancer CenterBillings, United StatesTaking people
- University of Alabama at Birmingham Cancer CenterBirmingham, United StatesTaking people
- Sanford Bismarck Medical CenterBismarck, United StatesTaking people
- Illinois CancerCare-BloomingtonBloomington, United StatesTaking people
- Saint Alphonsus Cancer Care Center-BoiseBoise, United StatesTaking people
- Beth Israel Deaconess Medical CenterBoston, United StatesTaking people
- Dana-Farber Cancer InstituteBoston, United StatesTaking people
- Bozeman Health Deaconess HospitalBozeman, United StatesTaking people
- Essentia Health Saint Joseph's Medical CenterBrainerd, United StatesTaking people
- Trinity Health IHA Medical Group Hematology Oncology - BrightonBrighton, United StatesTaking people
- Minnesota Oncology - BurnsvilleBurnsville, United StatesTaking people
- Saint Alphonsus Cancer Care Center-CaldwellCaldwell, United StatesTaking people
- Illinois CancerCare-CantonCanton, United StatesTaking people
- Trinity Health IHA Medical Group Hematology Oncology - CantonCanton, United StatesTaking people
- Saint Francis Medical CenterCape Girardeau, United StatesTaking people
- Saint Anthony Regional HospitalCarroll, United StatesTaking people
- Illinois CancerCare-CarthageCarthage, United StatesTaking people
- Mercy HospitalCedar Rapids, United StatesTaking people
- Oncology Associates at Mercy Medical CenterCedar Rapids, United StatesTaking people
- Cancer Center of Kansas - ChanuteChanute, United StatesTaking people
- UNC Lineberger Comprehensive Cancer CenterChapel Hill, United StatesTaking people
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea HospitalChelsea, United StatesTaking people
- Jefferson Cherry Hill HospitalCherry Hill, United StatesTaking people
- Northwestern UniversityChicago, United StatesTaking people
- University of IllinoisChicago, United StatesTaking people
- Siteman Cancer Center at Saint Peters HospitalCity of Saint Peters, United StatesTaking people
- Cleveland Clinic Cancer Center/Fairview HospitalCleveland, United StatesTaking people
- Cleveland Clinic FoundationCleveland, United StatesTaking people
- UI Health Care Mission Cancer and Blood - West Des Moines ClinicClive, United StatesTaking people
- Kootenai Health - Coeur d'AleneCoeur d'Alene, United StatesTaking people
- Baptist Memorial Hospital and Cancer Center-ColliervilleCollierville, United StatesTaking people
- Memorial Hospital NorthColorado Springs, United StatesTaking people
- UCHealth Memorial Hospital CentralColorado Springs, United StatesTaking people
- Columbus Oncology and Hematology Associates IncColumbus, United StatesTaking people
- Doctors HospitalColumbus, United StatesTaking people
- Grant Medical CenterColumbus, United StatesTaking people
- Ohio State University Comprehensive Cancer CenterColumbus, United StatesTaking people
- Riverside Methodist HospitalColumbus, United StatesTaking people
- Mercy HospitalCoon Rapids, United StatesTaking people
- UM Sylvester Comprehensive Cancer Center at Coral GablesCoral Gables, United StatesTaking people
- UM Sylvester Comprehensive Cancer Center at Coral SpringsCoral Springs, United StatesTaking people
- Siteman Cancer Center at West County HospitalCreve Coeur, United StatesTaking people
- Carle at The RiverfrontDanville, United StatesTaking people
- Geisinger Medical CenterDanville, United StatesTaking people
- Cancer Care Specialists of Illinois - DecaturDecatur, United StatesTaking people
- Decatur Memorial HospitalDecatur, United StatesTaking people
- Essentia Health - Deer River ClinicDeer River, United StatesTaking people
- UM Sylvester Comprehensive Cancer Center at Deerfield BeachDeerfield Beach, United StatesTaking people
- Delaware Health Center-Grady Cancer CenterDelaware, United StatesTaking people
- Grady Memorial HospitalDelaware, United StatesTaking people
- Kaiser Permanente-FranklinDenver, United StatesTaking people
- Broadlawns Medical CenterDes Moines, United StatesTaking people
- Iowa Methodist Medical CenterDes Moines, United StatesTaking people
- Mercy Medical Center - Des MoinesDes Moines, United StatesTaking people
- UI Health Care Mission Cancer and Blood - Des Moines ClinicDes Moines, United StatesTaking people
- UI Health Care Mission Cancer and Blood - Laurel ClinicDes Moines, United StatesTaking people
- Wayne State University/Karmanos Cancer InstituteDetroit, United StatesTaking people
- Illinois CancerCare-DixonDixon, United StatesTaking people
- Cancer Center of Kansas - Dodge CityDodge City, United StatesTaking people
- UM Sylvester Comprehensive Cancer Center at DoralDoral, United StatesTaking people
- Columbus Oncology and Hematology AssociatesDublin, United StatesTaking people
- Dublin Methodist HospitalDublin, United StatesTaking people
- Kaiser Permanente DublinDublin, United StatesTaking people
- Essentia Health Cancer CenterDuluth, United StatesTaking people
- Duke University Medical CenterDurham, United StatesTaking people
- Minnesota Oncology - EdinaEdina, United StatesTaking people
- Swedish Cancer Institute-EdmondsEdmonds, United StatesTaking people
- Carle Physician Group-EffinghamEffingham, United StatesTaking people
- Cancer Center of Kansas - El DoradoEl Dorado, United StatesTaking people
- Illinois CancerCare-EurekaEureka, United StatesTaking people
- Essentia Health Cancer Center-South University ClinicFargo, United StatesTaking people
- Sanford Broadway Medical CenterFargo, United StatesTaking people
- Sanford Roger Maris Cancer CenterFargo, United StatesTaking people
- Parkland Health Center - FarmingtonFarmington, United StatesTaking people
- Weisberg Cancer Treatment CenterFarmington Hills, United StatesTaking people
- Kaiser Permanente-FontanaFontana, United StatesTaking people
- McFarland Clinic - Trinity Cancer CenterFort Dodge, United StatesTaking people
- UI Healthcare Mission Cancer and Blood - Fort DodgeFort Dodge, United StatesTaking people
- Kaiser Permanente-FremontFremont, United StatesTaking people
- Kaiser Permanente Fresno Orchard PlazaFresno, United StatesTaking people
- Illinois CancerCare-GalesburgGalesburg, United StatesTaking people
- Glens Falls HospitalGlens Falls, United StatesNo longer taking part
- Grand Valley OncologyGrand Junction, United StatesTaking people
- Benefis Sletten Cancer InstituteGreat Falls, United StatesTaking people
- Saint Vincent Hospital Cancer Center at Saint Mary'sGreen Bay, United StatesTaking people
- Saint Vincent Hospital Cancer Center Green BayGreen Bay, United StatesTaking people
- Kaiser Permanente South BayHarbor City, United StatesTaking people
- HaysMedHays, United StatesTaking people
- Margaret R Pardee Memorial HospitalHendersonville, United StatesTaking people
- Essentia Health Hibbing ClinicHibbing, United StatesTaking people
- UM Sylvester Comprehensive Cancer Center at HollywoodHollywood, United StatesTaking people
- Kaiser Permanente Moanalua Medical CenterHonolulu, United StatesTaking people
- Cancer Center of Kansas-IndependenceIndependence, United StatesTaking people
- Kaiser Permanente-IrvineIrvine, United StatesTaking people
- Swedish Cancer Institute-IssaquahIssaquah, United StatesNo longer taking part
- Jersey City Medical CenterJersey City, United StatesTaking people
- Jupiter Medical CenterJupiter, United StatesTaking people
- Logan Health Medical CenterKalispell, United StatesTaking people
- University Health Truman Medical CenterKansas City, United StatesTaking people
- University of Kansas Cancer CenterKansas City, United StatesTaking people
- University of Kansas Cancer Center - BriarcliffKansas City, United StatesTaking people
- University of Kansas Cancer Center - NorthKansas City, United StatesTaking people
- Illinois CancerCare-Kewanee ClinicKewanee, United StatesTaking people
- Cancer Center of Kansas-KingmanKingman, United StatesTaking people
- Gundersen Lutheran Medical CenterLa Crosse, United StatesTaking people
- Kaiser Permanente-Rock CreekLafayette, United StatesTaking people
- The Watson ClinicLakeland, United StatesTaking people
- University of Michigan Health - Sparrow LansingLansing, United StatesTaking people
- Lawrence Memorial HospitalLawrence, United StatesTaking people
- University of Kansas Cancer Center - Lee's SummitLee's Summit, United StatesTaking people
- Cancer Center of Kansas-LiberalLiberal, United StatesTaking people
- Cooperman Barnabas Medical CenterLivingston, United StatesTaking people
- Trinity Health Saint Mary Mercy Livonia HospitalLivonia, United StatesTaking people
- Kaiser Permanente-Lone TreeLone Tree, United StatesTaking people
- Monmouth Medical CenterLong Branch, United StatesTaking people
- Cedars-Sinai Medical CenterLos Angeles, United StatesTaking people
- Kaiser Permanente Los Angeles Medical CenterLos Angeles, United StatesTaking people
- Kaiser Permanente West Los AngelesLos Angeles, United StatesTaking people
- The James Graham Brown Cancer Center at University of LouisvilleLouisville, United StatesTaking people
- UofL Health Medical Center NortheastLouisville, United StatesTaking people
- Illinois CancerCare-MacombMacomb, United StatesTaking people
- William S Middleton VA Medical CenterMadison, United StatesTaking people
- OhioHealth Mansfield HospitalMansfield, United StatesTaking people
- OhioHealth Marion General HospitalMarion, United StatesTaking people
- McFarland Clinic - MarshalltownMarshalltown, United StatesTaking people
- Carle Physician Group-Mattoon/CharlestonMattoon, United StatesTaking people
- Hillcrest Hospital Cancer CenterMayfield Heights, United StatesTaking people
- Cancer Center of Kansas - McPhersonMcPherson, United StatesTaking people
- Baptist Memorial Hospital and Cancer Center-MemphisMemphis, United StatesTaking people
- Idaho Urologic Institute-MeridianMeridian, United StatesTaking people
- UM Sylvester Comprehensive Cancer Center at KendallMiami, United StatesTaking people
- University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, United StatesTaking people
- Mount Sinai Medical CenterMiami Beach, United StatesTaking people
- Abbott-Northwestern HospitalMinneapolis, United StatesTaking people
- Community Medical CenterMissoula, United StatesTaking people
- Avera Cancer Institute - MitchellMitchell, United StatesTaking people
- Kaiser Permanente- Modesto MOB IIModesto, United StatesTaking people
- Ochsner LSU Health Monroe Medical CenterMonroe, United StatesTaking people
- ProHealth D N Greenwald CenterMukwonago, United StatesTaking people
- Saint Alphonsus Cancer Care Center-NampaNampa, United StatesTaking people
- Rutgers Cancer Institute of New JerseyNew Brunswick, United StatesTaking people
- Mount Sinai HospitalNew York, United StatesTaking people
- Helen F Graham Cancer CenterNewark, United StatesTaking people
- Medical Oncology Hematology Consultants PANewark, United StatesTaking people
- Providence Newberg Medical CenterNewberg, United StatesTaking people
- Cancer Center of Kansas - NewtonNewton, United StatesTaking people
- Carle BroMenn Medical CenterNormal, United StatesTaking people
- Carle Cancer Institute NormalNormal, United StatesTaking people
- University of Miami Sylvester Comprehensive Cancer Center at Sole MiaNorth Miami, United StatesTaking people
- Cancer Care Center of O'FallonO'Fallon, United StatesTaking people
- HSHS Saint Elizabeth's HospitalO'Fallon, United StatesTaking people
- Kaiser Permanente-OaklandOakland, United StatesTaking people
- ProHealth Oconomowoc Memorial HospitalOconomowoc, United StatesTaking people
- Saint Vincent Hospital Cancer Center at Oconto FallsOconto Falls, United StatesTaking people
- University of Oklahoma Health Sciences CenterOklahoma City, United StatesTaking people
- The University of Kansas Cancer Center - OlatheOlathe, United StatesTaking people
- Kaiser Permanente-OntarioOntario, United StatesTaking people
- Saint Alphonsus Cancer Care Center-OntarioOntario, United StatesTaking people
- Providence Willamette Falls Medical CenterOregon City, United StatesTaking people
- Illinois CancerCare-Ottawa ClinicOttawa, United StatesTaking people
- University of Kansas Cancer Center-Overland ParkOverland Park, United StatesTaking people
- Kaiser Permanente - Panorama CityPanorama City, United StatesTaking people
- Cancer Center of Kansas - ParsonsParsons, United StatesTaking people
- Illinois CancerCare-PekinPekin, United StatesTaking people
- UI Healthcare Mission Cancer and Blood - PellaPella, United StatesTaking people
- Illinois CancerCare-PeoriaPeoria, United StatesTaking people
- Illinois CancerCare-PeruPeru, United StatesTaking people
- Jefferson Torresdale HospitalPhiladelphia, United StatesTaking people
- Thomas Jefferson University HospitalPhiladelphia, United StatesTaking people
- OhioHealth Pickerington Methodist HospitalPickerington, United StatesTaking people
- Avera Cancer Institute at PierrePierre, United StatesTaking people
- UM Sylvester Comprehensive Cancer Center at PlantationPlantation, United StatesTaking people
- Trinity Health Saint Joseph Mercy Oakland HospitalPontiac, United StatesTaking people
- Kaiser Permanente NorthwestPortland, United StatesTaking people
- MaineHealth Maine Medical Center - PortlandPortland, United StatesTaking people
- Providence Portland Medical CenterPortland, United StatesTaking people
- Providence Saint Vincent Medical CenterPortland, United StatesTaking people
- Kootenai Clinic Cancer Services - Post FallsPost Falls, United StatesTaking people
- Cancer Center of Kansas - PrattPratt, United StatesTaking people
- Illinois CancerCare-PrincetonPrinceton, United StatesTaking people
- Rhode Island HospitalProvidence, United StatesTaking people
- VCU Massey Comprehensive Cancer CenterRichmond, United StatesTaking people
- Kaiser Permanente-RiversideRiverside, United StatesTaking people
- Mayo Clinic in RochesterRochester, United StatesTaking people
- University of RochesterRochester, United StatesTaking people
- UW Health Carbone Cancer Center RockfordRockford, United StatesTaking people
- Kaiser Permanente-RosevilleRoseville, United StatesTaking people
- Kaiser Permanente Downtown CommonsSacramento, United StatesTaking people
- Kaiser Permanente-South SacramentoSacramento, United StatesTaking people
- Park Nicollet Clinic - Saint Louis ParkSaint Louis Park, United StatesTaking people
- Regions HospitalSaint Paul, United StatesTaking people
- United HospitalSaint Paul, United StatesTaking people
- Sainte Genevieve County Memorial HospitalSainte Genevieve, United StatesTaking people
- Cancer Center of Kansas - SalinaSalina, United StatesTaking people
- Salina Regional Health CenterSalina, United StatesTaking people
- Kaiser Permanente-San Diego ZionSan Diego, United StatesTaking people
- Kaiser Permanente-San FranciscoSan Francisco, United StatesTaking people
- Kaiser Permanente-Santa Teresa-San JoseSan Jose, United StatesTaking people
- Kaiser Permanente San LeandroSan Leandro, United StatesTaking people
- Kaiser Permanente-San MarcosSan Marcos, United StatesTaking people
- Kaiser San Rafael-GallinasSan Rafael, United StatesTaking people
- Kootenai Clinic Cancer Services - SandpointSandpoint, United StatesTaking people
- Essentia Health SandstoneSandstone, United StatesTaking people
- Kaiser Permanente Medical Center - Santa ClaraSanta Clara, United StatesTaking people
- Kaiser Permanente-Santa RosaSanta Rosa, United StatesTaking people
- Swedish Medical Center-First HillSeattle, United StatesTaking people
- Sidney Kimmel Cancer Center Washington TownshipSewell, United StatesTaking people
- Memorial Hospital EastShiloh, United StatesTaking people
- LSU Health Sciences Center at ShreveportShreveport, United StatesTaking people
- Avera Cancer InstituteSioux Falls, United StatesTaking people
- Sanford Cancer Center Oncology ClinicSioux Falls, United StatesTaking people
- Sanford USD Medical Center - Sioux FallsSioux Falls, United StatesTaking people
- MaineHealth Cancer Care and IV Therapy - South PortlandSouth Portland, United StatesTaking people
- Kaiser Permanente-South San FranciscoSouth San Francisco, United StatesTaking people
- Baptist Memorial Hospital and Cancer Center-DesotoSouthhaven, United StatesTaking people
- Southern Illinois University School of MedicineSpringfield, United StatesTaking people
- Springfield ClinicSpringfield, United StatesTaking people
- Springfield Memorial HospitalSpringfield, United StatesTaking people
- Missouri Baptist Medical CenterSt Louis, United StatesTaking people
- Siteman Cancer Center at Christian HospitalSt Louis, United StatesTaking people
- Siteman Cancer Center-South CountySt Louis, United StatesTaking people
- Washington University School of MedicineSt Louis, United StatesTaking people
- Saint Vincent Hospital Cancer Center at Sturgeon BaySturgeon Bay, United StatesTaking people
- Missouri Baptist Sullivan HospitalSullivan, United StatesTaking people
- VCU Health Tappahannock HospitalTappahannock, United StatesTaking people
- University of Kansas Health System Saint Francis CampusTopeka, United StatesTaking people
- Carle Cancer CenterUrbana, United StatesTaking people
- Kaiser Permanente-VallejoVallejo, United StatesTaking people
- Essentia Health Virginia ClinicVirginia, United StatesTaking people
- Kaiser Permanente-Walnut CreekWalnut Creek, United StatesTaking people
- Illinois CancerCare - WashingtonWashington, United StatesTaking people
- UI Health Care Mission Cancer and Blood - Waukee ClinicWaukee, United StatesTaking people
- UW Cancer Center at ProHealth CareWaukesha, United StatesTaking people
- Wilmot Cancer Institute at WebsterWebster, United StatesTaking people
- Cancer Center of Kansas - WellingtonWellington, United StatesTaking people
- OhioHealth Westerville Medical Campus/Westerville Cancer CenterWesterville, United StatesTaking people
- University of Kansas Hospital-Westwood Cancer CenterWestwood, United StatesTaking people
- Ascension Via Christi Hospitals WichitaWichita, United StatesTaking people
- Cancer Center of Kansas - WichitaWichita, United StatesTaking people
- Cancer Center of Kansas-Wichita Medical Arts TowerWichita, United StatesTaking people
- Geisinger Wyoming Valley/Henry Cancer CenterWilkes-Barre, United StatesTaking people
- Cancer Center of Kansas - WinfieldWinfield, United StatesTaking people
- Fairview Cancer Center - WoodburyWoodbury, United StatesTaking people
- Kaiser Permanente-Woodland HillsWoodland Hills, United StatesTaking people
- Avera Cancer Institute at YanktonYankton, United StatesTaking people
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor CampusYpsilanti, United StatesTaking people
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- Alliance for Clinical Trials in Oncology
- Trial code
- NCT07321652
- Record updated
- 3 November 2026
- Original description
This phase III trial compares the effect of adding sonrotoclax to zanubrutinib versus zanubrutinib alone for the treatment of patients with untreated chronic lymphoblastic leukemia (CLL)/small lymphocytic lymphoma (SLL). Sonrotoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Zanubrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantel cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Giving sonrotoclax and zanubrutinib may be more effective than zanubrutinib alone for the treatment of untreated CLL/SLL.Read full original descriptionShow less
Phase III Evaluation of Fixed Duration Zanubrutinib Plus Sonrotoclax-Based Therapy Compared to Continuous Zanubrutinib in Previously Untreated Older Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
This phase III trial compares the effect of adding sonrotoclax to zanubrutinib versus zanubrutinib alone for the treatment of patients with untreated chronic lymphoblastic leukemia (CLL)/small lymphocytic lymphoma (SLL). Sonrotoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Zanubrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantel cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Giving sonrotoclax and zanubrutinib may be more effective than zanubrutinib alone for the treatment of untreated CLL/SLL.
Inclusion: STEP 0: This bone marrow or peripheral blood submission to Adaptive is mandatory prior to registration/randomization for real-time identification of the clone needed for MRD testing. The bone marrow sample should be from the first aspiration (i.e., first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be obtained as soon after pre-registration as possible to confirm registration eligibility; STEP 0: Patients must be diagnosed with CLL/SLL according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria that includes all of the following:; ≥ 5 x10\^9 /L B lymphocytes (5000/μL) in the peripheral blood (CLL) or a lymph node biopsy demonstrating SLL with the below immunophenotype (SLL); On morphologic review, the leukemic cells must be small mature lymphocytes; Immunophenotype of CLL cells (performed locally) must reveal a clonal B-cell population, which coexpress the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5. Patients with bright surface immunoglobulin expression or lack of CD23 expression in > 10% of cells must lack t(11;14) translocation by interphase cytogenetics; STEP 0: Patients must meet criteria for treatment as defined by IWCLL 2018 guidelines which includes at least one of the following criteria:; Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia), typically hemoglobin (Hb) < 10 g/dL, platelet count < 100,000/mm\^3; Massive (> 6 cm below the costal margin), progressive or symptomatic splenomegaly; Massive nodes (ie, > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy; Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy; Constitutional symptoms, which include any of the following:; Unintentional weight loss of ≥ 10% within the previous 6 months; Significant fatigue (ie. Eastern Cooperative Oncology Group [ECOG] performance status [PS] ≥ 2); Fevers >100.5 °F or 38.0°C for 2 weeks or more without evidence of infection; Night sweats > 1 month without evidence of infection; STEP 0: Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids); STEP 0: Treatment with rituximab and/or high-dose corticosteroids for autoimmune complications of CLL must be completed prior to enrollment. Palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration; STEP 0: Age ≥ 65 years; STEP 0: ECOG performance status ≤ 2; STEP 0: Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial; STEP 0: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated; STEP 0: Patients with a history of hepatitis C virus (HCV), infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load; STEP 0: Patients must not be receiving active systemic anticoagulation with warfarin. Patients must be off warfarin therapy for at least 5 half-lives washout and with normal INR prior to enrollment; STEP 0: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better; Patients with acute cardiac events within 6 months prior to registration should be carefully evaluated for their suitability for enrollment; STEP 0: No patients with a history of a severe bleeding disorder or a history of hemorrhagic stroke or intracranial hemorrhage; STEP 0: No patients with known active progressive central nervous system (CNS) disease; STEP 0: No known medical condition causing an inability to swallow oral formulations of agents; STEP 1: The adaptive report confirming a measurable and trackable B cell clone; STEP 1: Patients may not have had major surgery within 7 days of enrollment, or minor surgery within 5 days of enrollment. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. The decision about whether a surgery is major or minor can be made at the discretion of the treating physician; STEP 1: No patients with ongoing active fungal, bacterial or viral infection requiring systemic therapy except those described in the protocol document; STEP 1: Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily; STEP 1: Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics; STEP 1: Patients must not have continued requirement for therapy with a strong CYP3A4/5 inhibitor or inducer. Any such inhibitor or inducer must have been discontinued at least 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug; STEP 1: Absolute neutrophil count (ANC) ≥ 1,000/mm3 unless due to marrow involvement; STEP 1: Platelet count ≥ 30,000/mm3; STEP 1: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless due to liver involvement, hemolysis or Gilbert's disease); STEP 1: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3.0 x upper limit of normal (ULN) unless due to disease infiltration of the liver; STEP 1: Calculated (calc.) creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) ≥ 30 mL/min; STEP 1: Urine protein to creatinine ratio < 1 or urine protein ≤ 1+; STEP 2: Detectable MRD ≥ 10 residual clonal cells per million nucleated cells in peripheral blood at the C15 restaging evaluation from ClonoSEQ; STEP 2: Response of PR, PR-L, CR, CCR or CRi to zanubrutinib sonrotoclax therapy.