AzTrials
AzTrials

Chronic Lymphocytic LeukemiaPhase 3NCT03737981

Testing the Addition of a New Anti-cancer Drug, Venetoclax, to the Usual Treatment (Ibrutinib and Obinutuzumab) in Untreated, Older Patients With Chronic Lymphocytic Leukemia

A Phase 3 study testing Ibrutinib, Obinutuzumab and Observation Activity in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by National Cancer Institute (NCI) at 857 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial summary

This phase III trial compares adding a new anti-cancer drug (venetoclax) to the usual treatment (ibrutinib plus obinutuzumab) in older patients with chronic lymphocytic leukemia who have not received previous treatment. Read more about this study

Who is it for?
Ages 65 years and older
What is being tested?
Ibrutinib, Obinutuzumab and Observation Activity
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
465 participants
Where
857 sitesUnited States
Study dates
31 Jan 2019to 29 Dec 2026
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • PRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 0)
  • Patients must have been diagnosed with chronic lymphocytic leukemia (CLL) (> 5000 B-cells per uL of peripheral blood at any point during the course of their disease) or small lymphocytic lymphoma (SLL) with < 5000 B-cells per uL of blood but with disease-associated lymphadenopathy
  • This blood submission is mandatory prior to registration/randomization to perform fluorescence in situ hybridization (FISH) centrally that will be used for stratification. It should be obtained as soon after pre-registration as possible
  • REGISTRATION ELIGIBILITY CRITERIA (STEP 1)
  • Patients must be diagnosed with CLL or SLL in accordance with 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria that includes all of the following:
  • >= 5 x10^9 B lymphocytes (5000/uL) in the peripheral blood measured by flow cytometry at any point in the course of the disease or less peripheral blood involvement but disease-associated lymphadenopathy
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  • On local morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes
  • Neoplastic cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express 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
  • Patients must be intermediate or high-risk Rai stage CLL or SLL
  • Intermediate risk (formerly stage I/II) is defined by lymphadenopathy and/or hepatomegaly or splenomegaly without anemia or thrombocytopenia
  • High risk (formerly stage III/IV) is defined by splenomegaly and/or anemia (hemoglobin < 11g/dL) not attributable to autoimmune hemolytic anemia and/or thrombocytopenia (platelets [plt] < 100 x10^9/L) not attributable to autoimmune thrombocytopenia
  • Patients must meet criteria for treatment as defined by 2018 IWCLL 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)
  • Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
  • Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy
  • Progressive lymphocytosis with a lymphocyte doubling time < 6 months or an increase of >= 50% over a 2 month period
  • Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
  • Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, spine)
  • Constitutional symptoms, which include any of the following:
  • Unintentional weight loss of 10% or more within 6 months
  • Significant fatigue
  • Fevers > 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
  • Night sweats >= 1 month without evidence of infection
  • Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL/SLL must be complete at least 4 weeks 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
  • Age >= 65 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1,000/mm^3 except if due to bone marrow involvement
  • Platelet count (untransfused) >= 30,000/mm^3 except if due to bone marrow involvement
  • Calculated (Calc.) creatinine clearance >= 40 mL/min (by Cockcroft-Gault)
  • Bilirubin =< 1.5 x upper limit of normal (ULN) except if due to liver involvement, hemolysis, or Gilbert's disease
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) except if due to liver involvement
  • If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
  • Please note: Intravenous immunoglobulin therapy (IVIG) can cause a false positive hepatitis B serology. If patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B deoxyribonucleic acid [DNA]) they may still participate in the study, must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician
  • If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
  • Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Central fluorescent in situ hybridization (FISH) blood results are mandatory prior to registration/randomization for it will be used for stratification
  • Patients must be able to swallow capsules and not have the following conditions: disease significantly affecting gastrointestinal absorption, resection of the stomach or small bowel, partial or complete bowel obstruction
  • Patients must be able to receive either a xanthine oxidase inhibitor or rasburicase for prophylaxis/treatment of tumor lysis syndrome (TLS)
  • RE-REGISTRATION ELIGIBILITY CRITERIA (STEP 2)
  • Completion of treatment through cycle 14 day 28, and remain on ibrutinib therapy
  • Receipt of central BM MRD results
  • Response assessment completed with CR determination

Who cannot join

  • Patients must not have had prior therapy for CLL/SLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)
  • Patients must not have any history of Richter's transformation or prolymphocytic leukemia (prolymphocytes in blood > 55%)
  • Patients with class III or class IV heart failure by New York Heart Association, those with unstable angina, and those with uncontrolled arrhythmia are not eligible
  • Patients who have had a myocardial infarction, intracranial bleed, or stroke within the past 6 months are not eligible
  • Patients must not be receiving active systemic anticoagulation with heparin or warfarin. Patients on warfarin must discontinue the drug for at least 10 days prior to registration on the study
  • Chronic concomitant treatment with strong inhibitors of CYP3A4/5 is not allowed on this study. Patients on strong CYP3A inhibitors must discontinue the drug for 14 days prior to registration on the study
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  • Chronic concomitant treatment with strong CYP3A4/5 inducers is not allowed. Patients must discontinue the drug 14 days prior to registration on the study
  • Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily
  • Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics
  • Patients must not have a known allergy to mannitol
  • Patients must not have prior significant hypersensitivity to rituximab (not including infusion reactions)
  • Patients may not have had major surgery within 10 days prior to registration, or minor surgery within 7 days prior to registration. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration for a joint. The decision about whether a surgery is major or minor can be made at the discretion of the treating physician

Trial locations and contacts

857 sites in 1 country.

300 sites in 1 country

United States300 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Queen's Cancer Center - Pearlridge

    ‘Aiea, Hawaii, 96701

  • The Cancer Center of Hawaii-Pali Momi

    ‘Aiea, Hawaii, 96701

  • Avera Cancer Institute-Aberdeen

    Aberdeen, South Dakota, 57401

  • Providence Regional Cancer System-Aberdeen

    Aberdeen, Washington, 98520

  • Riverwood Healthcare Center

    Aitkin, Minnesota, 56431

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Christus Saint Frances Cabrini Hospital

    Alexandria, Louisiana, 71301

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • OSF Saint Anthony's Health Center

    Alton, Illinois, 62002

  • The Don and Sybil Harrington Cancer Center

    Amarillo, Texas, 79106

  • American Fork Hospital / Huntsman Intermountain Cancer Center

    American Fork, Utah, 84003

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Community Hospital of Anaconda

    Anaconda, Montana, 59711

  • Kaiser Permanente-Anaheim

    Anaheim, California, 92806

  • Anchorage Associates in Radiation Medicine

    Anchorage, Alaska, 98508

  • Anchorage Radiation Therapy Center

    Anchorage, Alaska, 99504

  • Alaska Breast Care and Surgery LLC

    Anchorage, Alaska, 99508

  • Alaska Oncology and Hematology LLC

    Anchorage, Alaska, 99508

  • Alaska Women's Cancer Care

    Anchorage, Alaska, 99508

  • Anchorage Oncology Centre

    Anchorage, Alaska, 99508

  • Katmai Oncology Group

    Anchorage, Alaska, 99508

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Aspirus Cancer Care-Antigo-Volm Cancer Center

    Antigo, Wisconsin, 54409

  • ThedaCare Regional Cancer Center

    Appleton, Wisconsin, 54911

  • Ascension Northeast Wisconsin-Saint Elizabeth Cancer Center-Appleton

    Appleton, Wisconsin, 54915

  • Mission Hope Medical Oncology - Arroyo Grande

    Arroyo Grande, California, 93420

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Messino Cancer Centers

    Asheville, North Carolina, 28806

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • Northwest Wisconsin Cancer Center

    Ashland, Wisconsin, 54806

  • University Cancer and Blood Center LLC

    Athens, Georgia, 30607

  • Hematology Oncology Associates of Central New York-Auburn

    Auburn, New York, 13021

  • MultiCare Auburn Medical Center

    Auburn, Washington, 98001

  • Augusta Oncology Associates PC-D'Antignac

    Augusta, Georgia, 30901

  • Augusta Oncology Associates PC-Wheeler

    Augusta, Georgia, 30909

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • Rocky Mountain Cancer Centers-Aurora

    Aurora, Colorado, 80012

  • The Medical Center of Aurora

    Aurora, Colorado, 80012

  • Rocky Mountain Regional VA Medical Center

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Virginia Mason Bainbridge Island Medical Center

    Bainbridge Island, Washington, 98110

  • Saint Alphonsus Cancer Care Center-Baker City

    Baker City, Oregon, 97814

  • Kaiser Permanente-Baldwin Park

    Baldwin Park, California, 91706

  • Mercy Oncology and Hematology - Clayton-Clarkson

    Ballwin, Missouri, 63011

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Saint Agnes Hospital

    Baltimore, Maryland, 21229

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • CommonSpirit Saint Joseph Hospital - Bardstown

    Bardstown, Kentucky, 40004

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Indu and Raj Soin Medical Center

    Beavercreek, Ohio, 45431

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • Overlake Medical Center

    Bellevue, Washington, 98004

  • Kaiser Permanente-Bellflower

    Bellflower, California, 90706

  • PeaceHealth Saint Joseph Medical Center

    Bellingham, Washington, 98225

  • Strecker Cancer Center-Belpre

    Belpre, Ohio, 45714

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Saint Charles Health System

    Bend, Oregon, 97701

  • Lehigh Valley Hospital - Muhlenberg

    Bethlehem, Pennsylvania, 18017

  • University of Iowa Healthcare Cancer Services Quad Cities

    Bettendorf, Iowa, 52722

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Saint Vincent Frontier Cancer Center

    Billings, Montana, 59102

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Saint Joseph's/Candler - Bluffton Campus

    Bluffton, South Carolina, 29910

  • Saint Elizabeth Boardman Hospital

    Boardman, Ohio, 44512

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • Parkland Health Center-Bonne Terre

    Bonne Terre, Missouri, 63628

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Boulder Community Foothills Hospital

    Boulder, Colorado, 80303

  • Rocky Mountain Cancer Centers-Boulder

    Boulder, Colorado, 80304

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Cox Cancer Center Branson

    Branson, Missouri, 65616

  • Lafayette Family Cancer Center-EMMC

    Brewer, Maine, 04412

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Ascension Southeast Wisconsin Hospital-Elmbrook Campus-Brookfield

    Brookfield, Wisconsin, 53045

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Saint Joseph Regional Cancer Center

    Bryan, Texas, 77802

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Saint Anne Hospital

    Burien, Washington, 98166

  • Lahey Clinic

    Burlington, Massachusetts, 01805

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Minnesota Oncology - Burnsville

    Burnsville, Minnesota, 55337

  • Loyola Center for Health at Burr Ridge

    Burr Ridge, Illinois, 60527

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Cambridge Medical Center

    Cambridge, Minnesota, 55008

  • Hematology Oncology Associates of CNY at Camillus

    Camillus, New York, 13031

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Mercy Cancer Center - Cape Girardeau

    Cape Girardeau, Missouri, 63703

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Memorial Hospital of Carbondale

    Carbondale, Illinois, 62902

  • Caro Cancer Center

    Caro, Michigan, 48723

  • Carson Tahoe Regional Medical Center

    Carson City, Nevada, 89703

  • SIH Cancer Institute

    Carterville, Illinois, 62918

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Waverly Hematology Oncology

    Cary, North Carolina, 27518

  • Sandra L Maxwell Cancer Center

    Cedar City, Utah, 84720

  • Physicians' Clinic of Iowa PC

    Cedar Rapids, Iowa, 52402

  • Rocky Mountain Cancer Centers - Centennial

    Centennial, Colorado, 80112

  • Dayton Physicians LLC-Miami Valley South

    Centerville, Ohio, 45459

  • Miami Valley Hospital South

    Centerville, Ohio, 45459

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Providence Regional Cancer System-Centralia

    Centralia, Washington, 98531

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • Chambersburg Hospital

    Chambersburg, Pennsylvania, 17201

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Geauga Hospital

    Chardon, Ohio, 44024

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Memorial Hospital

    Chattanooga, Tennessee, 37404

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Cheyenne Regional Medical Center-West

    Cheyenne, Wyoming, 82001

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Ascension Calumet Hospital-Chilton

    Chilton, Wisconsin, 53014

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Oncology Hematology Care Inc-Kenwood

    Cincinnati, Ohio, 45236

  • Bethesda North Hospital

    Cincinnati, Ohio, 45242

  • TriHealth Cancer Institute-Westside

    Cincinnati, Ohio, 45247

  • TriHealth Cancer Institute-Anderson

    Cincinnati, Ohio, 45255

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • Hematology Oncology Consultants-Clarkston

    Clarkston, Michigan, 48346

  • Newland Medical Associates-Clarkston

    Clarkston, Michigan, 48346

  • Wake Forest University at Clemmons

    Clemmons, North Carolina, 27012

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Southeastern Medical Oncology Center-Clinton

    Clinton, North Carolina, 28328

  • Prisma Health Cancer Institute - Laurens

    Clinton, South Carolina, 29325

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Community Cancer Institute

    Clovis, California, 93611

  • University Oncology Associates

    Clovis, California, 93611

  • Billings Clinic-Cody

    Cody, Wyoming, 82414

  • Kootenai Health - Coeur d'Alene

    Coeur d'Alene, Idaho, 83814

  • Coffeyville Regional Medical Center

    Coffeyville, Kansas, 67337

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Rocky Mountain Cancer Centers-Penrose

    Colorado Springs, Colorado, 80907

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Mount Carmel East Hospital

    Columbus, Ohio, 43213

  • Columbus Oncology and Hematology Associates Inc

    Columbus, Ohio, 43214

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Grant Medical Center

    Columbus, Ohio, 43215

  • The Mark H Zangmeister Center

    Columbus, Ohio, 43219

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

  • Doctors Hospital

    Columbus, Ohio, 43228

  • New Hampshire Oncology Hematology PA-Concord

    Concord, New Hampshire, 03301

  • Cookeville Regional Medical Center

    Cookeville, Tennessee, 38501

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Bay Area Hospital

    Coos Bay, Oregon, 97420

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Commonwealth Cancer Center-Corbin

    Corbin, Kentucky, 40701

  • UC Irvine Health Cancer Center-Newport

    Costa Mesa, California, 92627

  • Alegent Health Mercy Hospital

    Council Bluffs, Iowa, 51503

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • UPMC Western Maryland

    Cumberland, Maryland, 21502

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Dayton Physician LLC - Englewood

    Dayton, Ohio, 45415

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Dayton Veterans Affairs Medical Center

    Dayton, Ohio, 45428

  • Corewell Health Dearborn Hospital

    Dearborn, Michigan, 48124

  • Henry Ford Medical Center-Fairlane

    Dearborn, Michigan, 48126

  • Atlanta VA Medical Center

    Decatur, Georgia, 30033

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • Broward Health North

    Deerfield Beach, Florida, 33064

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Delaware Health Center-Grady Cancer Center

    Delaware, Ohio, 43015

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Cancer Center of Colorado at Sloan's Lake

    Denver, Colorado, 80204

  • Denver Health Medical Center

    Denver, Colorado, 80204

  • Kaiser Permanente-Franklin

    Denver, Colorado, 80205

  • National Jewish Health-Main Campus

    Denver, Colorado, 80206

  • The Women's Imaging Center

    Denver, Colorado, 80209

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Presbyterian - Saint Lukes Medical Center - Health One

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Midtown

    Denver, Colorado, 80218

  • Saint Joseph Hospital - Cancer Centers of Colorado

    Denver, Colorado, 80218

  • Rocky Mountain Cancer Centers-Rose

    Denver, Colorado, 80220

  • Rose Medical Center

    Denver, Colorado, 80220

  • Western Surgical Care

    Denver, Colorado, 80220

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Henry Ford Health Saint John Hospital

    Detroit, Michigan, 48236

  • Essentia Health Saint Mary's - Detroit Lakes Clinic

    Detroit Lakes, Minnesota, 56501

  • Illinois CancerCare-Dixon

    Dixon, Illinois, 61021

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Dublin Methodist Hospital

    Dublin, Ohio, 43016

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • CommonSpirit Cancer Center Mercy

    Durango, Colorado, 81301

  • Mercy Medical Center

    Durango, Colorado, 81301

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Prisma Health Cancer Institute - Easley

    Easley, South Carolina, 29640

  • Henry Ford River District Hospital

    East China Township, Michigan, 48054

  • The Cancer Institute at Saint Francis Hospital

    East Hills, New York, 11548

  • Pocono Medical Center

    East Stroudsburg, Pennsylvania, 18301

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • HSHS Sacred Heart Hospital

    Eau Claire, Wisconsin, 54701

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • STCC at DHR Health Institute for Research and Development

    Edinburg, Texas, 78539

  • Swedish Cancer Institute-Edmonds

    Edmonds, Washington, 98026

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Walter Knox Memorial Hospital

    Emmett, Idaho, 83617

  • Mountain Blue Cancer Care Center - Swedish

    Englewood, Colorado, 80113

  • Rocky Mountain Cancer Centers - Swedish

    Englewood, Colorado, 80113

  • Swedish Medical Center

    Englewood, Colorado, 80113

  • The Melanoma and Skin Cancer Institute

    Englewood, Colorado, 80113

  • Saint Elizabeth Hospital

    Enumclaw, Washington, 98022

  • Ephrata Cancer Center

    Ephrata, Pennsylvania, 17522

  • Ephrata Community Hospital

    Ephrata, Pennsylvania, 17522

  • OSF Saint Francis Hospital and Medical Group

    Escanaba, Michigan, 49829

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

  • Fairbanks Memorial Hospital

    Fairbanks, Alaska, 99701

  • Smilow Cancer Hospital Care Center-Fairfield

    Fairfield, Connecticut, 06824

  • Essentia Health Cancer Center-South University Clinic

    Fargo, North Dakota, 58103

  • Sanford South University Medical Center

    Fargo, North Dakota, 58103

  • Sanford Medical Center Fargo

    Fargo, North Dakota, 58104

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Parkland Health Center - Farmington

    Farmington, Missouri, 63640

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Corewell Health Farmington Hills Hospital

    Farmington Hills, Michigan, 48336

  • Virginia Mason Federal Way Medical Center

    Federal Way, Washington, 98002

  • Saint Francis Hospital

    Federal Way, Washington, 98003

  • Lake Region Healthcare Corporation-Cancer Care

    Fergus Falls, Minnesota, 56537

  • Armes Family Cancer Center

    Findlay, Ohio, 45840

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • Orion Cancer Care

    Findlay, Ohio, 45840

  • Cancer Hematology Centers - Flint

    Flint, Michigan, 48503

  • Genesee Hematology Oncology PC

    Flint, Michigan, 48503

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • Hurley Medical Center

    Flint, Michigan, 48503

  • Aurora Health Center-Fond du Lac

    Fond du Lac, Wisconsin, 54937

  • Kaiser Permanente-Fontana

    Fontana, California, 92335

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • Holy Cross Hospital

    Fort Lauderdale, Florida, 33308

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Mercy Hospital Fort Smith

    Fort Smith, Arkansas, 72903

  • UT Southwestern/Simmons Cancer Center-Fort Worth

    Fort Worth, Texas, 76104

  • Essentia Health - Fosston

    Fosston, Minnesota, 56542

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Dayton Physicians LLC-Atrium

    Franklin, Ohio, 45005

  • Ascension Southeast Wisconsin Hospital - Franklin

    Franklin, Wisconsin, 53132

  • Reiman Cancer Center-Ascension Wisconsin Health Center-Rawson

    Franklin, Wisconsin, 53132

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • Central Ohio Breast and Endocrine Surgery

    Gahanna, Ohio, 43230

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • Central Care Cancer Center - Garden City

    Garden City, Kansas, 67846

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Adams Cancer Center

    Gettysburg, Pennsylvania, 17325

  • Tacoma/Valley Radiation Oncology Centers-Gig Harbor

    Gig Harbor, Washington, 98332

  • MultiCare Gig Harbor Medical Park

    Gig Harbor, Washington, 98335

  • Smilow Cancer Hospital Care Center at Glastonbury

    Glastonbury, Connecticut, 06033

  • Glens Falls Hospital

    Glens Falls, New York, 12801

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

Other trials in United States

About this study

Official title: A Randomized Phase III Study of Ibrutinib Plus Obinutuzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients (&gt;/= 65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)

This phase III trial compares adding a new anti-cancer drug (venetoclax) to the usual treatment (ibrutinib plus obinutuzumab) in older patients with chronic lymphocytic leukemia who have not received previous treatment. The addition of venetoclax to the usual treatment might prevent chronic lymphocytic leukemia from returning. This trial also will investigate whether patients who receive ibrutinib plus obinutuzumab plus venetoclax and have no detectable chronic lymphocytic leukemia after 1 year of treatment, can stop taking ibrutinib. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Venetoclax 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. Giving ibrutinib and obinutuzumab with venetoclax may work better at treating chronic lymphocytic leukemia compared to ibrutinib and obinutuzumab.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare the progression-free survival (PFS) between control treatment and experimental treatment strategies: ibrutinib/obinutuzumab (IO) with ibrutinib maintenance (IM) versus ibrutinib/venetoclax/obinutuzumab (IVO) regardless of IM or observation.

SECONDARY OBJECTIVES:

  1. To compare bone marrow (BM) minimal residual disease (MRD)- complete response (CR) rates, MRD- rates, and depth of response at cycle 15 day 1 between patients treated with IO versus IVO.

II. To compare overall survival (OS) between the control and experimental treatment strategies: IO with IM versus IVO regardless of IM or observation.

III. To compare the 5-year PFS and overall survival (OS) for the control and experimental treatment strategies: IO with IM versus IVO regardless of IM or observation.

IV. To describe the toxicity profile for each of the treatment strategies and by each treatment course.

CORRELATIVES SCIENCE OBJECTIVES:

  1. To compare MRD status between blood and bone marrow at the end of induction treatment/cycle 15 day 1 to determine whether blood MRD can be used as a surrogate to bone marrow MRD with these treatment regimens.

II. To compare peripheral blood MRD status by standard central flow cytometry to next generation sequencing (NGS) using ClonoSeq technique to determine the agreement in MRD negativity of the two techniques.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Patients also receive obinutuzumab intravenously (IV) on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Treatment repeats every 28 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 15, patients receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive ibrutinib PO QD on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Beginning cycle 3, patients also receive venetoclax PO QD on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity. All patients will then receive a 15th cycle of ibrutinib. Beginning cycle 16, patients who do not achieve a BM MRD negative CR, receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a BM MRD negative CR undergo observation every 3 cycles for 6 years, then every 6 cycles thereafter.

After completion of study treatment, patients are followed every 6 months until 10 years from registration.

Being tested
Ibrutinib, Obinutuzumab, Observation Activity, Venetoclax
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765

    Given PO

  • ObinutuzumabBiological

    Also called Anti-CD20 Monoclonal Antibody R7159, GA 101, GA-101, GA101

    Given IV

  • Observation ActivityOther

    Also called Observation

    Undergo observation

  • VenetoclaxDrug

    Also called ABT 199, ABT-0199, ABT-199, ABT199

    Given PO

Study groups in NCT03737981
Study groupRoleWhat they receive
Arm I (ibrutinib, obinutuzumab)Active comparatorPatients receive ibrutinib PO QD on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Treatment repeats every 28 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 15, patients receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Ibrutinib; Biological: Obinutuzumab
Arm II (ibrutinib, obinutuzumab, venetoclax)ExperimentalPatients receive ibrutinib PO QD on days 1-28. Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of cycle 1, and on day 1 of cycles 2-6. Beginning cycle 3, patients also receive venetoclax PO QD on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity. All patients will then receive a 15th cycle of ibrutinib. Beginning cycle 16, patients who do not achieve a BM MRD negative CR, receive ibrutinib PO QD every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a BM MRD negative CR undergo observation every 3 cycles for 6 years, then every 6 cycles thereafter.
Receives: Drug: Ibrutinib; Biological: Obinutuzumab; Other: Observation Activity; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS)

    PFS will be compared between the experimental and control treatment strategy groups using a stratified log-rank test (stratified on Rai stage, intermediate versus [vs.] high, and del(17p13.1) by fluorescence in situ hybridization [FISH], present vs. absent). The Kaplan-Meier method will be used to estimate PFS distributions. Five-year PFS estimates and corresponding hazard ratios will be provided with 95% confidence intervals for each treatment strategy.

    Measured: 5 years

Secondary outcomes (3)

  1. Bone Marrow (BM) Minimal Residual Disease (MRD)- Complete Response (CR) Rate

    BM MRD- CR rate will be calculated and will be estimated using the number of patients meeting the BM MRD- CR criteria divided by the total number of patients randomized to each of the treatment arms. The stratified Cochran-Mantel-Haenszel test will be used to compare the BM MRD- CR rates between treatment arms (stratified on Rai stage, intermediate vs. high, and del(17p13.1) by FISH, present vs. absent).

    Measured: Up to 10 years

  2. Overall Survival (OS)

    The Kaplan-Meier method will be used to estimate the OS distribution for each treatment strategy. Estimates at 5 years will be calculated with corresponding 95% confidence intervals, and differences in these estimates between the treatment strategies will be tested using a stratified chi-square test based on the complementary log-log transformation of the Kaplan-Meier estimates. Comparisons in OS curves between experimental and control treatment strategies will use a stratified log-rank test (stratified on Rai stage, intermediate vs. high, and del(17p13.1) by FISH, present vs. absent). Hazard ratios with 95% confidence intervals will be estimated from the corresponding, stratified proportional hazard model.

    Measured: From randomization date until death from any cause, assessed up to 10 years

  3. Incidence of Adverse Events

    Will be defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment, graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Frequency and severity of adverse events and tolerability for each treatment strategy group will be summarized using descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. The incidence of severe (grade 3+) adverse events or toxicities will be described.

    Measured: Up to 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2018
  2. Study start31 Jan 2019
  3. Primary completion17 Jan 2025
  4. Study completion29 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
465 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03737981
Sponsor's protocol ID
NCI-2018-02485
Other IDs
NCI-2018-02485, A041702, A041702, U10CA180821
Status last verified
Jul 2026
First submitted
9 Nov 2018
Last updated
22 Oct 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

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