Testing the Effects of Novel Therapeutics for Newly Diagnosed, Untreated Patients With High-Risk Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)
Purpose
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.
Conditions
- Acute Myeloid Leukemia
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
- Acute Myeloid Leukemia Post Cytotoxic Therapy
- Acute Myeloid Leukemia, Myelodysplasia-Related
Eligibility
- Eligible Ages
- Between 18 Years and 59 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- STEP 1 REGISTRATION:
- Participants must have been registered to Master Screening and Re-Assessment
Protocol, MYELOMATCH, prior to consenting to this study. Participants must have been
assigned to this clinical trial, via MATCHBox, prior to registration to this study.
- Note: Pre-enrollment/diagnosis labs must have already been performed under the
MYELOMATCH
- Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) per
World Health Organization (WHO) criteria
- Participants must have high-risk (adverse) AML per European LeukemiaNet (ELN) 2017
criteria
- Participants with therapy-related AML (t-AML), or with AML evolving from an
antecedent hematologic disorder (such as myeloproliferative neoplasm), or AML with
myelodysplasia-related changes (AML-MRC) are eligible
- Acute promyelocytic leukemia is excluded
- Participants with favorable or intermediate risk disease are excluded
- Participants with FLT3 mutations (ITD or TKD) are excluded
- Participants with t(9;22) translocation are excluded
- A single dose of intrathecal chemotherapy is allowed prior to study entry
- Prior anthracycline therapy is allowed but must not exceed a cumulative lifetime
dose of 200 mg/m^2 daunorubicin or equivalent. Prior hypomethylating agent (HMA)
exposure is allowed, as long as not for AML diagnosis
- Participants must not have received or be currently receiving any prior therapy for
acute myeloid leukemia. Hydroxyurea to control the white blood cells (WBC) is
allowed prior to registration and initiation of protocol-defined therapy. All trans
retinoic acid (ATRA) given until a diagnosis of acute promyelocytic leukemia is
ruled out is also allowed.
- Participants must not be receiving or planning to receive any other investigational
agents before completing protocol therapy
- Participants must be between 18 and 59 years of age
- Participants must have Zubrod performance status =< 3 as determined by a history and
physical (H&P) completed within 14 days prior to registration
- Participants must have a complete medical history and physical exam within 7 days
prior to registration
- Participants must be able to swallow and retain oral medications and have no known
gastrointestinal disorders likely to interfere with absorption of oral medications
- Participants with known human immunodeficiency virus (HIV)-infection must be on
effective anti-retroviral therapy at time of registration and have undetectable HIV
viral load within 6 months prior to registration
- Participants with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load within 28 days prior to registration and be on
suppressive therapy, if indicated
- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. Participants with active HCV infection who are currently on
treatment must have an undetectable HCV viral load within 28 days prior to
registration
- The following tests must be performed within 14 days prior to registration to
establish baseline values:
- Complete blood count (CBC)/differential/platelets
- Total bilirubin
- Lactate dehydrogenase (LDH)
- Albumin
- Glucose
- Fibrinogen
- Participants must have adequate kidney function as evidenced by creatinine clearance
>= 30mL/min (by Cockcroft Gault) within 28 days prior to registration
- Participants must have adequate liver function as evidenced by aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of
normal (ULN), and total bilirubin =< 2.0 x ULN (or 5.0 x ULN if the participant has
a history of Gilbert's disease) within 28 days prior to registration
- Total bilirubin =< 2.0 x ULN (or 5.0 x ULN if the participant has a history of
Gilbert's disease) within 28 days prior to registration
- Participants must have adequate cardiac function as determined by echocardiography
or MUGA scan with an ejection fraction >= 50% within 28 days prior to registration
- Participants with a prior or concurrent malignancy whose natural history (in the
opinion of the treating physician) does not have the potential to interfere with the
safety or efficacy assessment of the investigational regimen are eligible for this
trial. No concurrent therapies for such malignancy are allowed with the exception of
hormonal therapy
- Participants with known history of Wilson's disease or other known copper-metabolism
disorder are excluded
- Participants must not be pregnant or nursing. Women/men of reproductive potential
must have agreed to use 2 contraception methods. A woman is considered to be of
"reproductive potential" if she has had menses at any time in the preceding 12
consecutive months. In addition to routine contraceptive methods (e.g., hormonal
contraceptives [examples include birth control pills, vaginal rings, or patches]
associated with inhibition of ovulation for at least 1 month prior to taking study
drug), "effective contraception" also includes heterosexual celibacy and surgery
intended to prevent pregnancy (or with a side-effect of pregnancy prevention)
defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation.
However, if at any point a previously celibate participant chooses to become
heterosexually active during the time period for use of contraceptive measures
outlined in the protocol, he/she is responsible for beginning contraceptive
measures. A barrier method should be used during this study along with hormonal
contraceptives from initial study drug administration to 30 days after the last dose
of study drug as drug-drug interaction with venetoclax is unknown
- Participants must have agreed to have specimens submitted for translational medicine
(MRD) under the myeloMATCH MSRP and specimens must be submitted
- Participants must be informed of the investigational nature of this study and must
sign and give informed consent in accordance with institutional and federal
guidelines
- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has
been entered in the system
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm I (cytarabine, daunorubicin) |
Patients receive cytarabine 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 ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. |
|
|
Experimental Arm II (cytarabine, daunorubicin, venetoclax) |
Patients receive cytarabine IV continuously on days 2-8 and daunorubicin IV on days 2-4 with venetoclax 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. |
|
|
Experimental Arm III (azacitidine, venetoclax) |
Patients receive azacitidine 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. |
|
|
Experimental Arm IV (daunorubicin and cytarabine liposome) |
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. |
|
|
Experimental Arm V (daunorubicin and cytarabine liposome, venetoclax) |
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. |
|
Recruiting Locations
Birmingham, Alabama 35233
Phoenix, Arizona 85054
Site Public Contact
855-776-0015
Tucson, Arizona 85719
Tucson, Arizona 85719
Little Rock, Arkansas 72205
Site Public Contact
501-686-8274
Berkeley, California 94704
Los Angeles, California 90048
Site Public Contact
310-423-8965
Sacramento, California 95817
Site Public Contact
916-734-3089
San Francisco, California 94143
Site Public Contact
877-827-3222
San Mateo, California 94401
New Haven, Connecticut 06520
Jacksonville, Florida 32224-9980
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855-776-0015
Augusta, Georgia 30912
'Aiea, Hawaii 96701
'Aiea, Hawaii 96701
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808-486-6000
Honolulu, Hawaii 96813
Honolulu, Hawaii 96813
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808-522-4333
Honolulu, Hawaii 96826
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808-983-6090
Boise, Idaho 83706
Boise, Idaho 83712
Caldwell, Idaho 83605
Coeur d'Alene, Idaho 83814
Fruitland, Idaho 83619
Meridian, Idaho 83642
Nampa, Idaho 83687
Nampa, Idaho 83687
Post Falls, Idaho 83854
Sandpoint, Idaho 83864
Bloomington, Illinois 61701
Bloomington, Illinois 61704
Canton, Illinois 61520
Carthage, Illinois 62321
Chicago, Illinois 60611
Chicago, Illinois 60637
Decatur, Illinois 62526
Decatur, Illinois 62526
Dixon, Illinois 61021
Site Public Contact
815-285-7800
Effingham, Illinois 62401
Eureka, Illinois 61530
Evanston, Illinois 60201
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847-570-2109
Galesburg, Illinois 61401
Glenview, Illinois 60026
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847-570-2109
Highland Park, Illinois 60035
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847-570-2109
Kewanee, Illinois 61443
Macomb, Illinois 61455
Maywood, Illinois 60153
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708-226-4357
O'Fallon, Illinois 62269
Ottawa, Illinois 61350
Pekin, Illinois 61554
Peoria, Illinois 61615
Peoria, Illinois 61636
Peoria, Illinois 61637
Peru, Illinois 61354
Princeton, Illinois 61356
Springfield, Illinois 62702
Site Public Contact
217-545-7929
Springfield, Illinois 62702
Site Public Contact
800-444-7541
Springfield, Illinois 62781
Washington, Illinois 61571
Indianapolis, Indiana 46202
Iowa City, Iowa 52242
Site Public Contact
800-237-1225
Fairway, Kansas 66205
Kansas City, Kansas 66160
Overland Park, Kansas 66211
Westwood, Kansas 66205
Lexington, Kentucky 40536
Site Public Contact
859-257-3379
Louisville, Kentucky 40202
Site Public Contact
502-562-3429
Louisville, Kentucky 40245
Baton Rouge, Louisiana 70805
Baton Rouge, Louisiana 70808
Site Public Contact
225-765-7659
Portland, Maine 04102
South Portland, Maine 04106
Baltimore, Maryland 21287
Boston, Massachusetts 02111
Burlington, Massachusetts 01805
Peabody, Massachusetts 01960
Ann Arbor, Michigan 48106
Brighton, Michigan 48114
Canton, Michigan 48188
Chelsea, Michigan 48118
Detroit, Michigan 48201
Detroit, Michigan 48202
Farmington Hills, Michigan 48334
Flint, Michigan 48503
Flint, Michigan 48503
Flint, Michigan 48503
Flint, Michigan 48503
Livonia, Michigan 48154
Novi, Michigan 48377
West Bloomfield, Michigan 48322
Ypsilanti, Michigan 48197
Deer River, Minnesota 56636
Duluth, Minnesota 55805
Hibbing, Minnesota 55746
Site Public Contact
218-786-3308
Minneapolis, Minnesota 55407
Rochester, Minnesota 55905
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855-776-0015
Saint Paul, Minnesota 55101
Saint Paul, Minnesota 55102
Sandstone, Minnesota 55072
Virginia, Minnesota 55792
Columbus, Mississippi 39705
Grenada, Mississippi 38901
New Albany, Mississippi 38652
Oxford, Mississippi 38655
Southhaven, Mississippi 38671
Creve Coeur, Missouri 63141
Saint Louis, Missouri 63110
Saint Louis, Missouri 63129
Saint Louis, Missouri 63136
Saint Peters, Missouri 63376
Anaconda, Montana 59711
Billings, Montana 59101
Bozeman, Montana 59715
Great Falls, Montana 59405
Kalispell, Montana 59901
Missoula, Montana 59804
Bellevue, Nebraska 68123
Omaha, Nebraska 68118
Site Public Contact
402-559-5600
Omaha, Nebraska 68198
Henderson, Nevada 89052
Las Vegas, Nevada 89102
Las Vegas, Nevada 89148
Livingston, New Jersey 07039
Long Branch, New Jersey 07740
New Brunswick, New Jersey 08903
Site Public Contact
732-235-7356
Paramus, New Jersey 07652
Ridgewood, New Jersey 07450
Toms River, New Jersey 08755
Albuquerque, New Mexico 87106
Bronx, New York 10467
Buffalo, New York 14263
Lake Success, New York 11042
Site Public Contact
516-734-8896
Manhasset, New York 11030
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516-734-8896
New York, New York 10029
Rochester, New York 14642
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585-275-5830
Syracuse, New York 13210
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315-464-5476
Charlotte, North Carolina 28203
Site Public Contact
800-804-9376
Durham, North Carolina 27710
Site Public Contact
888-275-3853
Columbus, Ohio 43210
Oklahoma City, Oklahoma 73104
Ontario, Oregon 97914
Portland, Oregon 97213
Portland, Oregon 97225
Portland, Oregon 97239
Allentown, Pennsylvania 18103
Danville, Pennsylvania 17822
Hershey, Pennsylvania 17033-0850
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19107
Pittsburgh, Pennsylvania 15232
Site Public Contact
412-647-8073
West Reading, Pennsylvania 19611
Site Public Contact
610-988-9323
Boiling Springs, South Carolina 29316
Easley, South Carolina 29640
Greenville, South Carolina 29605
Greenville, South Carolina 29605
Greenville, South Carolina 29615
Greer, South Carolina 29650
Seneca, South Carolina 29672
Collierville, Tennessee 38017
Knoxville, Tennessee 37920
Site Public Contact
865-544-9773
Memphis, Tennessee 38120
Salt Lake City, Utah 84112
Burlington, Vermont 05401
Burlington, Vermont 05405
Charlottesville, Virginia 22908
Fairfax, Virginia 22031
Falls Church, Virginia 22042
Edmonds, Washington 98026
Issaquah, Washington 98029
Seattle, Washington 98122
Appleton, Wisconsin 54911
Ashland, Wisconsin 54806
Green Bay, Wisconsin 54301
Green Bay, Wisconsin 54303
La Crosse, Wisconsin 54601
Milwaukee, Wisconsin 53226
Site Public Contact
414-805-3666
San Juan, Puerto Rico 00927
San Juan, Puerto Rico 00936
Site Public Contact
787-763-1296
More Details
- NCT ID
- NCT05554406
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
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. BAKING 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 first year, every 2 months for the second year, every 3 months for the third year and every 6 months to year 5.