Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)
Start Date
9/13/2024
Completion Date
12/31/2027
Summary
This phase II MyeloMATCH treatment trial compares cytarabine with daunorubicin versus cytarabine with daunorubicin and venetoclax versus venetoclax with azacitidine for the treatment of younger patients with intermediate risk acute myeloid leukemia (AML). Cytarabine is a drug that inhibits some of the enzymes needed for deoxyribonucleic acid (DNA) replication and repair and can slow or stop the growth of cancer cells. Daunorubicin is a drug that blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. 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. Azacitidine is a drug that interacts with DNA to activate tumor-suppressing genes, resulting in an anti-tumor effect. Adding venetoclax to cytarabine and daunorubicin, and adding venetoclax to azacitidine, may work better than the usual treatment of cytarabine with daunorubicin alone. To decide if they are better, the study doctors are looking to see if venetoclax increases the rate of elimination of AML in participants by 20% or more compared to the usual approach.
Detailed Description
PRIMARY OBJECTIVE: I. To compare the rates of undetectable measurable residual disease (MRD) in patients who achieve a complete remission (CR) after induction therapy with 7 +3 (cytarabine + daunorubicin hydrochloride \[daunorubicin\]) versus (vs.) azacitidine + venetoclax vs. 7+3 + venetoclax. SECONDARY OBJECTIVES: I. To estimate the frequency and severity of toxicities with each of the regimens. II. To estimate complete remission (CR) rates (with and without MRD), complete remission with incomplete count recovery (CRi) (with and without MRD) rates, event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS) with each of the regimens. TERTIARY OBJECTIVES: I. To evaluate response to therapy received according to genomic findings. II. To evaluate MRD kinetics by following patients with detectable MRD through Tier 2 and beyond. III. To evaluate longer term outcomes by treatment arm, genomics, MRD outcome, and other features as patients receive additional myeloMATCH therapies to generate testable hypotheses for more precise patient selection for these therapies. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive daunorubicin intravenously (IV) on days 2-4, cytarabine IV continuously on days 2-8, and venetoclax orally (PO) once per day (QD) on days 1-11. Cycle is 28 days and treatment is given in the absence of disease progression or unacceptable toxicity. Based on a bone marrow aspiration assessment (completed at the discretion of the treating investigator), patients may receive reinduction consisting of daunorubicin IV on days 2-3, cytarabine IV continuously on days 2-6, and venetoclax PO QD on days 1-8. Cycle is 28 days and treatment is given in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated. ARM II: Patients receive azacitidine IV or subcutaneously (SC) on days 1-7 or days 1-5 and 8-9 and venetoclax PO on days 1-28 of each cycle. Cycles repeat every 28 days for a total of 2 cycles, in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated. ARM III: Patients receive daunorubicin IV on days 1-3 and cytarabine IV, continuously, on days 1-7. Cycle is 28 days and treatment is given in the absence of disease progression or unacceptable toxicity. Based on a bone marrow aspiration assessment (completed at the discretion of the treating investigator), patients may receive reinduction consisting of cytarabine IV, continuously, on days 1-5 and daunorubicin IV on days 1-2. Cycle is 28 days and treatment is given in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and collection of blood samples on study and as clinically indicated. After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 1 year every 6 months for the second year and yearly thereafter.
Eligibility Criteria
Age Range: 18 years to 59 years
Interventions
Azacitidine
Biospecimen Collection
Bone Marrow Aspiration
Cytarabine
Daunorubicin Hydrochloride
Venetoclax
Conditions
Locations
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233
United States
Banner University Medical Center - Tucson
Tucson, Arizona 85719
United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona 85719
United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California 94704
United States
Cedars-Sinai Medical Center
Los Angeles, California 90048
United States
UCSF Medical Center-Parnassus
San Francisco, California 94143
United States
Miami Cancer Institute
Miami, Florida 33176
United States
Memorial Hospital West
Pembroke Pines, Florida 33028
United States
Phoebe Putney Memorial Hospital
Albany, Georgia 31701
United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho 83706
United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho 83712
United States
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho 83605
United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho 83814
United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho 83619
United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho 83642
United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho 83687
United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho 83687
United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho 83854
United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho 83864
United States
Centralia Oncology Clinic
Centralia, Illinois 62801
United States
Northwestern University
Chicago, Illinois 60611
United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637
United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois 62526
United States
Decatur Memorial Hospital
Decatur, Illinois 62526
United States
Crossroads Cancer Center
Effingham, Illinois 62401
United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois 60201
United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois 60026
United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois 60035
United States
Loyola University Medical Center
Maywood, Illinois 60153
United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois 60451
United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois 62269
United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois 60462
United States
Southern Illinois University School of Medicine
Springfield, Illinois 62702
United States
Springfield Clinic
Springfield, Illinois 62702
United States
Springfield Memorial Hospital
Springfield, Illinois 62781
United States
UChicago Medicine Northwest Indiana
Crown Point, Indiana 46307
United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa 52242
United States
University of Kansas Clinical Research Center
Fairway, Kansas 66205
United States
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas 66211
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky 40202
United States
UofL Health Medical Center Northeast
Louisville, Kentucky 40245
United States
LSU Health Baton Rouge-North Clinic
Baton Rouge, Louisiana 70805
United States
Our Lady of the Lake Physician Group
Baton Rouge, Louisiana 70808
United States
Our Lady of The Lake
Baton Rouge, Louisiana 70808
United States
MaineHealth Maine Medical Center - Portland
Portland, Maine 04102
United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine 04074
United States
MaineHealth Cancer Care and IV Therapy - South Portland
South Portland, Maine 04106
United States
Walter Reed National Military Medical Center
Bethesda, Maryland 20889-5600
United States
Tufts Medical Center
Boston, Massachusetts 02111
United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215
United States
Lahey Clinic
Burlington, Massachusetts 01805
United States
Lahey Clinic Peabody
Peabody, Massachusetts 01960
United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan 48114
United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan 48188
United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan 48118
United States
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan 48038
United States
Henry Ford Hospital
Detroit, Michigan 48202
United States
Cancer Hematology Centers - Flint
Flint, Michigan 48503
United States
Genesee Hematology Oncology PC
Flint, Michigan 48503
United States
Genesys Hurley Cancer Institute
Flint, Michigan 48503
United States
Hurley Medical Center
Flint, Michigan 48503
United States
Allegiance Health
Jackson, Michigan 49201
United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan 48154
United States
Henry Ford Medical Center-Columbus
Novi, Michigan 48377
United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan 48341
United States
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan 48322
United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan 48197
United States
Mercy Hospital
Coon Rapids, Minnesota 55433
United States
Essentia Health - Deer River Clinic
Deer River, Minnesota 56636
United States
Essentia Health Cancer Center
Duluth, Minnesota 55805
United States
Fairview Southdale Hospital
Edina, Minnesota 55435
United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota 55746
United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota 55407
United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota 55416
United States
Regions Hospital
Saint Paul, Minnesota 55101
United States
United Hospital
Saint Paul, Minnesota 55102
United States
Essentia Health Sandstone
Sandstone, Minnesota 55072
United States
Essentia Health Virginia Clinic
Virginia, Minnesota 55792
United States
Baptist Memorial Hospital and Cancer Center-Golden Triangle
Columbus, Mississippi 39705
United States
Baptist Cancer Center-Grenada
Grenada, Mississippi 38901
United States
Baptist Memorial Hospital and Cancer Center-Union County
New Albany, Mississippi 38652
United States
Baptist Memorial Hospital and Cancer Center-Oxford
Oxford, Mississippi 38655
United States
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi 38671
United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376
United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri 63141
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Siteman Cancer Center-South County
St Louis, Missouri 63129
United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri 63136
United States
Community Hospital of Anaconda
Anaconda, Montana 59711
United States
Billings Clinic Cancer Center
Billings, Montana 59101
United States
Bozeman Health Deaconess Hospital
Bozeman, Montana 59715
United States
Benefis Sletten Cancer Institute
Great Falls, Montana 59405
United States
Logan Health Medical Center
Kalispell, Montana 59901
United States
Community Medical Center
Missoula, Montana 59804
United States
Nebraska Medicine-Bellevue
Bellevue, Nebraska 68123
United States
Nebraska Medicine-Village Pointe
Omaha, Nebraska 68118
United States
University of Nebraska Medical Center
Omaha, Nebraska 68198
United States
OptumCare Cancer Care at Charleston
Las Vegas, Nevada 89102
United States
OptumCare Cancer Care at Fort Apache
Las Vegas, Nevada 89183
United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire 03756
United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey 07920
United States
Saint Barnabas Medical Center
Livingston, New Jersey 07039
United States
Monmouth Medical Center
Long Branch, New Jersey 07740
United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey 07748
United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey 07645
United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey 08903
United States
The Valley Hospital - Luckow Pavilion
Paramus, New Jersey 07652
United States
Valley Health System Ridgewood Campus
Ridgewood, New Jersey 07450
United States
Community Medical Center
Toms River, New Jersey 08755
United States
University of New Mexico Cancer Center
Albuquerque, New Mexico 87106
United States
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Memorial Sloan Kettering Commack
Commack, New York 11725
United States
Mount Sinai Hospital
New York, New York 10029
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
University of Rochester
Rochester, New York 14642
United States
Stony Brook University Medical Center
Stony Brook, New York 11794
United States
Montefiore Medical Center - Moses Campus
The Bronx, New York 10467
United States
Memorial Sloan Kettering Nassau
Uniondale, New York 11553
United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina 28203
United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina 28204
United States
Duke University Medical Center
Durham, North Carolina 27710
United States
East Carolina University
Greenville, North Carolina 27834
United States
Novant Health Forsyth Medical Center
Winston-Salem, North Carolina 27103
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
United States
Case Western Reserve University
Cleveland, Ohio 44106
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon 97914
United States
Providence Portland Medical Center
Portland, Oregon 97213
United States
Providence Saint Vincent Medical Center
Portland, Oregon 97225
United States
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania 18103
United States
Geisinger Medical Center
Danville, Pennsylvania 17822
United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania 17033-0850
United States
Lewistown Hospital
Lewistown, Pennsylvania 17044
United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania 15232
United States
Reading Hospital
West Reading, Pennsylvania 19611
United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania 18711
United States
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina 29316
United States
Prisma Health Cancer Institute - Easley
Easley, South Carolina 29640
United States
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina 29605
United States
Prisma Health Cancer Institute - Faris
Greenville, South Carolina 29605
United States
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina 29615
United States
Prisma Health Cancer Institute - Greer
Greer, South Carolina 29650
United States
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina 29672
United States
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee 38017
United States
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee 38120
United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas 77030
United States
Ben Taub General Hospital
Houston, Texas 77030
United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112
United States
University of Vermont Medical Center
Burlington, Vermont 05401
United States
University of Vermont and State Agricultural College
Burlington, Vermont 05405
United States
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
Inova Schar Cancer Institute
Fairfax, Virginia 22031
United States
Inova Fairfax Hospital
Falls Church, Virginia 22042
United States
Swedish Cancer Institute-Edmonds
Edmonds, Washington 98026
United States
Swedish Cancer Institute-Issaquah
Issaquah, Washington 98029
United States
Swedish Medical Center-First Hill
Seattle, Washington 98122
United States
Duluth Clinic Ashland
Ashland, Wisconsin 54806
United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin 54301
United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin 54303
United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin 54601
United States
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin 54482
United States
Marshfield Medical Center - Weston
Weston, Wisconsin 54476
United States
Arthur J E Child Comprehensive Cancer Centre
Calgary, Alberta T2N 5G2
Canada
University of Alberta Hospital
Edmonton, Alberta T6G 2B7
Canada
CancerCare Manitoba
Winnipeg, Manitoba R3E 0V9
Canada
QEII Health Sciences Centre/Nova Scotia Health Authority
Halifax, Nova Scotia B3H 2Y9
Canada
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario L8V 5C2
Canada
Odette Cancer Centre- Sunnybrook Health Sciences Centre
Toronto, Ontario M4N 3M5
Canada
CSSS Champlain-Charles Le Moyne
Greenfield Park, Quebec J4V 2H1
Canada
CIUSSSEMTL-Hopital Maisonneuve-Rosemont
Montreal, Quebec H1T 2M4
Canada
Jewish General Hospital
Montreal, Quebec H3T 1E2
Canada
Centro Comprensivo de Cancer de UPR
San Juan, 00927
Puerto Rico
San Juan City Hospital
San Juan, 00936
Puerto Rico