A Randomized Phase II Study Comparing Cytarabine + Daunorubicin (7+3) vs (Daunorubicin and Cytarabine) Liposome, Cytarabine + Daunorubicin + Venetoclax, Azacitidine + Venetoclax, and (Daunorubicin and Cytarabine) Liposome + Venetoclax in Patients Aged 59 or Younger Who Are Considered High-Risk (Adverse) Acute Myeloid Leukemia As Determined by MYELOMATCH; A MYELOMATCH Clinical Trial
Summary
This phase II MyeloMATCH treatment trial tests whether the standard approach of cytarabine and daunorubicin in comparison to the following experimental regimens works to shrink cancer in patients with high risk acute myeloid leukemia (AML): 1) daunorubicin and cytarabine liposome alone; 2) cytarabine and daunorubicin with venetoclax; 3) azacitidine and venetoclax; 4) daunorubicin and cytarabine liposome and venetoclax. "High-risk" refers to traits that have been known to make the AML harder to treat. Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Daunorubicin is in a class of medications called anthracyclines. It also works by slowing or stopping the growth of cancer cells in the body. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal 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. There is evidence that these newer experimental treatment regimens may work better in getting rid of more AML compared to the standard approach of cytarabine and daunorubicin.
Detailed description
PRIMARY OBJECTIVE: I. To compare measurable residual disease (MRD) negative complete remission (CR) rates between each of the experimental regimens and cytarabine + daunorubicin (7+3). SECONDARY OBJECTIVES: I. To estimate the frequency and severity of toxicities with each of the regimens. II. To estimate complete remission (CR) rates, complete remission with incomplete count recovery (CRi, with and without MRD) rates, event-free survival (EFS), time to relapse, relapse-free survival (RFS), and overall survival (OS) with each of the regimens. III. To describe and compare MRD negative CR rates by genomic subgroups within and across randomized arms. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 5 arms. ARM I: Patients receive cytarabine intravenously (IV) continuously on days 1-7 and daunorubicin IV on days 1-3 per standard approach of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 1-5 and daunorubicin IV on days 1-2. Patients undergo echocardiography (ECHO) or multigated acquisition (MUGA) scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. ARM II: Patients receive cytarabine IV continuously on days 2-8 and daunorubicin IV on days 2-4 with venetoclax orally (PO) on days 1-11 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 2-6 and daunorubicin IV on days 2-3 with venetoclax PO on days 1-8. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. ARM III: Patients receive azacitidine subcutaneously (SC) or IV on days 1-7 and venetoclax PO on days 1-28 of each cycle. Cycles repeat every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. ARM IV: Patients receive daunorubicin and cytarabine liposome IV over 90 minutes on days 1, 3, and 5 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of daunorubicin and cytarabine liposome IV over 90 minutes on days 1 and 3. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. ARM V: Patients receive daunorubicin and cytarabine liposome IV over 90 minutes on days 1, 3, and 5 and venetoclax PO on days 1-14 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of daunorubicin and cytarabine liposome IV over 90 minutes on days 1 and 3 and venetoclax PO on days 1-7. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. After completion of study treatment, patients follow up every month for the first year, every 2 months for the second year, every 3 months for the third year and every 6 months to year 5.
Arms & interventions
- DrugAzacitidine
Given SC or IV
- ProcedureBiospecimen Collection
Undergo collection of blood
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- DrugCytarabine
Given IV
- DrugDaunorubicin Hydrochloride
Given IV
- ProcedureEchocardiography Test
Undergo ECHO
- DrugLiposome-encapsulated Daunorubicin-Cytarabine
Given IV
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- DrugVenetoclax
Given PO
Outcome measures
Primary
Minimal residual disease (MRD) response (Arm 1, 2, 4 and 5)
Will be analyzed using intent-to-treat (ITT) principles.
Time frame: After induction (28 days) or re-induction (56 days)
MRD response (Arm 3)
Will be analyzed using ITT principles.
Time frame: After two cycles of therapy (56 days)
Secondary
Early mortality
Time frame: On or before day 28
Time to count recovery
Time frame: After cycle 1 and cycle 2
Event-free survival
Time frame: From randomization to the first of: primary refractory disease; progressive disease; off protocol therapy without complete remission (CR) or CR with incomplete count recovery (CRi); relapse from CR or CRi, or death from any cause, assessed up to 5 years
Relapse-free survival
Time frame: From the date of achievement of a remission until the date of relapse or death from any cause, assessed up to 5 years
Overall survival
Time frame: From day of randomization on study until death from any cause, assessed up to 5 years
Time to relapse
Time frame: Up to 5 years
MRD negative complete remission (MRDneg CR)
Time frame: Up to 5 years
Incidence of adverse events
Time frame: Up to 5 years
Eligibility criteria
Study locations (211)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Mills Health Center
San Mateo, California, 94401
Yale University
New Haven, Connecticut, 06520
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Miami Cancer Institute
Miami, Florida, 33176
Memorial Hospital West
Pembroke Pines, Florida, 33028
Phoebe Putney Memorial Hospital
Albany, Georgia, 31701
Augusta University Medical Center
Augusta, Georgia, 30912
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu, Hawaii, 96813
Straub Clinic and Hospital
Honolulu, Hawaii, 96813
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Hawaii Cancer Care - Westridge
‘Aiea, Hawaii, 96701
Pali Momi Medical Center
‘Aiea, Hawaii, 96701
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
OSF Saint Joseph Medical Center
Bloomington, Illinois, 61701
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Illinois CancerCare-Canton
Canton, Illinois, 61520
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Northwestern University
Chicago, Illinois, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Crossroads Cancer Center
Effingham, Illinois, 62401
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, 60035
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Loyola University Medical Center
Maywood, Illinois, 60153
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, 61636
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Illinois CancerCare-Peru
Peru, Illinois, 61354
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Springfield Clinic
Springfield, Illinois, 62702
Springfield Memorial Hospital
Springfield, Illinois, 62781
Illinois CancerCare - Washington
Washington, Illinois, 61571
UChicago Medicine Northwest Indiana
Crown Point, Indiana, 46307
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
University of Kansas Cancer Center
Kansas City, Kansas, 66160
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202
UofL Health Medical Center Northeast
Louisville, Kentucky, 40245
LSU Health Baton Rouge-North Clinic
Baton Rouge, Louisiana, 70805
Our Lady of the Lake Physician Group
Baton Rouge, Louisiana, 70808
Our Lady of The Lake
Baton Rouge, Louisiana, 70808
MaineHealth Maine Medical Center - Portland
Portland, Maine, 04102
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, 04074
MaineHealth Cancer Care and IV Therapy - South Portland
South Portland, Maine, 04106
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Tufts Medical Center
Boston, Massachusetts, 02111
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805
Lahey Clinic Peabody
Peabody, Massachusetts, 01960
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
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
Allegiance Health
Jackson, Michigan, 49201
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Henry Ford Medical Center-Columbus
Novi, Michigan, 48377
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Mercy Hospital
Coon Rapids, Minnesota, 55433
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Fairview Southdale Hospital
Edina, Minnesota, 55435
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Essentia Health Sandstone
Sandstone, Minnesota, 55072
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792
Baptist Memorial Hospital and Cancer Center-Golden Triangle
Columbus, Mississippi, 39705
Baptist Cancer Center-Grenada
Grenada, Mississippi, 38901
Baptist Memorial Hospital and Cancer Center-Union County
New Albany, Mississippi, 38652
Baptist Memorial Hospital and Cancer Center-Oxford
Oxford, Mississippi, 38655
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi, 38671
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Community Hospital of Anaconda
Anaconda, Montana, 59711
Billings Clinic Cancer Center
Billings, Montana, 59101
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Logan Health Medical Center
Kalispell, Montana, 59901
Community Medical Center
Missoula, Montana, 59804
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123
Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118
University of Nebraska Medical Center
Omaha, Nebraska, 68198
OptumCare Cancer Care at Charleston
Las Vegas, Nevada, 89102
OptumCare Cancer Care at Fort Apache
Las Vegas, Nevada, 89183
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Cooper Hospital University Medical Center
Camden, New Jersey, 08103
Saint Barnabas Medical Center
Livingston, New Jersey, 07039
Monmouth Medical Center
Long Branch, New Jersey, 07740
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
The Valley Hospital - Luckow Pavilion
Paramus, New Jersey, 07652
Valley Health System Ridgewood Campus
Ridgewood, New Jersey, 07450
Community Medical Center
Toms River, New Jersey, 08755
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Roswell Park Cancer Institute
Buffalo, New York, 14263
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
North Shore University Hospital
Manhasset, New York, 11030
Mount Sinai Hospital
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Rochester
Rochester, New York, 14642
Stony Brook University Medical Center
Stony Brook, New York, 11794
State University of New York Upstate Medical University
Syracuse, New York, 13210
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Duke University Medical Center
Durham, North Carolina, 27710
East Carolina University
Greenville, North Carolina, 27834
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Case Western Reserve University
Cleveland, Ohio, 44106
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914
Providence Portland Medical Center
Portland, Oregon, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Oregon Health and Science University
Portland, Oregon, 97239
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Geisinger Medical Center
Danville, Pennsylvania, 17822
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Lewistown Hospital
Lewistown, Pennsylvania, 17044
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
Reading Hospital
West Reading, Pennsylvania, 19611
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711
Rhode Island Hospital
Providence, Rhode Island, 02903
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee, 38017
University of Tennessee - Knoxville
Knoxville, Tennessee, 37920
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
University of Vermont Medical Center
Burlington, Vermont, 05401
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029
Swedish Medical Center-First Hill
Seattle, Washington, 98122
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911
ThedaCare Regional Medical Center - Appleton
Appleton, Wisconsin, 54911
Duluth Clinic Ashland
Ashland, Wisconsin, 54806
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476