Brief 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.
Brief Title
Testing the Effects of Novel Therapeutics for Newly Diagnosed, Untreated Patients With High-Risk Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
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 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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Maximum Age
59 Years
Minimum Age
18 Years
NCT Id
NCT05554406
Org Class
Nih
Org Full Name
National Cancer Institute (NCI)
Org Study Id
NCI-2022-07535
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Description
Will be analyzed using intent-to-treat (ITT) principles.
Outcome Measure
Minimal residual disease (MRD) response (Arm 1, 2, 4 and 5)
Outcome Time Frame
After induction (28 days) or re-induction (56 days)
Outcome Description
Will be analyzed using intent-to-treat (ITT) principles.
Outcome Measure
Minimal residual disease (MRD) response (Arm 3)
Outcome Time Frame
After two cycles of therapy (56 days)
Secondary Ids
Secondary Id
NCI-2022-07535
Secondary Id
MM1YA-S01
Secondary Id
MM1YA-S01
Secondary Id
U10CA180888
Secondary Outcomes
Outcome Description
Will be assessed by death due to any cause between experimental arms and the 7+3 arm will be reported for each arm every DSMC cycle. Fisher's exact will be used to compare observed rates. A one-sided p-value \< 0.05 indicating increased early mortality rates in an experimental arm will be a threshold for termination of accrual to an arm due to increased early mortality.
Outcome Time Frame
On or before day 28
Outcome Measure
Early mortality
Outcome Description
Will be reported every DSMC cycle for the 7+3+venetoclax, (daunorubicin and cytarabine) liposome+venetoclax, and 7+3 arms. Median time to count recovery more than 7 days longer on either of the 7+3+venetoclax and (daunorubicin and cytarabine liposome+venetoclax arms compared to the 7+3 arm will be used a threshold to terminate accrual to an arm due to increased toxicity.
Outcome Time Frame
After cycle 1 and cycle 2
Outcome Measure
Time to count recovery
Outcome Description
Will be estimated using the Kaplan-Meier method.
Outcome 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
Outcome Measure
Event-free survival (EFS)
Outcome Description
Defined for only patients achieving complete remission (CR), or CR with incomplete hematologic recovery (CRi). Will be estimated using the Kaplan-Meier method.
Outcome 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
Outcome Measure
Relapse-free survival (RFS)
Outcome Description
Will be estimated using the Kaplan-Meier method.
Outcome Time Frame
From day of randomization on study until death from any cause, assessed up to 5 years
Outcome Measure
Overall survival (OS)
Outcome Description
Will be estimated with cumulative incidence curves with death without relapse analyzed a competing event. Response per 2017 European LeukemiaNet (ELN) guidelines will be tabulated and exact 95% confidence intervals will be calculated.
Outcome Time Frame
Up to 5 years
Outcome Measure
Time to relapse
Outcome Description
MRDneg CR rates will be tabulated by genomic subgroups within randomized arms and pooling arms. Rates across arms will be compared using Fisher's exact test. All p-values reported will be nominal.
Outcome Time Frame
Up to 5 years
Outcome Measure
MRD negative complete remission (MRDneg CR)
Outcome Description
Will be analyzed using National Cancer Institute Common Terminology Criteria for Adverse Events version (v) 5.0
Outcome Time Frame
Up to 5 years
Outcome Measure
Incidence of adverse events
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Maximum Age Number (converted to Years and rounded down)
59
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org