RecruitingNCT05554406ClinicalTrials.gov record

Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)

Acute Myeloid Leukemia · Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm · Acute Myeloid Leukemia Post Cytotoxic Therapy · Acute Myeloid Leukemia, Myelodysplasia-Related

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THE QUICK READ

What this study involves

The registry says this study is recruiting. Individual locations may have different availability.

Study type: Interventional
Phase: Phase 2
Age range: 18 years - 59 years
Sex eligible: All sexes
Healthy volunteers: Not accepted
Participants: 335 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

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.

Read the full 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.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

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 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-unless they were previously treated
Acute promyelocytic leukemia is excluded
Participants with favorable or intermediate risk disease per ELN 2017 criteria 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 for AML is allowed prior to study entry
Prior anthracycline therapy for any indication is allowed but must not exceed a cumulative lifetime dose of 200 mg/m\^2 daunorubicin or equivalent
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. For urgent cytoreduction, cytarabine may be given either as a single dose or in multiple doses not to exceed 2500 mg
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 complete medical history and physical exam (H\&P) completed 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 a known history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load on the most recent test results obtained within 6 months prior to registration
Participants with a known history 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 known 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 7 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) within 7 days prior to registration- unless elevations are considered due to leukemia in the opinion of the treating investigator
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 central nervous system (CNS) disease are eligible for this trial and will be treated according to institutional guidelines with intrathecal chemotherapy for this aspect of their disease.
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 MYELOMATCH and specimens must be submitted
Participants must be offered the opportunity to participate in specimen banking

Note: Specimens must be collected and submitted using the Southwest Oncology Group (SWOG) Specimen Tracking System
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

For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
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

Understand screening

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment: Random assignment
Masking: No masking

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.

Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Drug: Cytarabine · Drug: Daunorubicin Hydrochloride · Procedure: Echocardiography Test · Procedure: Multigated Acquisition Scan

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.

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.

Drug: Azacitidine · Procedure: Biospecimen Collection · Procedure: Echocardiography Test · Procedure: Multigated Acquisition Scan · Drug: Venetoclax

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.

Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Echocardiography Test · Drug: Liposome-encapsulated Daunorubicin-Cytarabine · Procedure: Multigated Acquisition Scan

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.

Azacitidine DRUG

Given SC or IV

Biospecimen Collection PROCEDURE

Undergo collection of blood

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Cytarabine DRUG

Given IV

Daunorubicin Hydrochloride DRUG

Given IV

Echocardiography Test PROCEDURE

Undergo ECHO

Liposome-encapsulated Daunorubicin-Cytarabine DRUG

Given IV

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Venetoclax DRUG

Given PO

Prepare your questions

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Minimal residual disease (MRD) response (Arm 1, 2, 4 and 5)

Time frame: After induction (28 days) or re-induction (56 days)

Will be analyzed using intent-to-treat (ITT) principles.

MRD response (Arm 3)

Time frame: After two cycles of therapy (56 days)

Will be analyzed using ITT principles.

Secondary measures

Early mortality

Time frame: On or before day 28

Will be assessed by death due to any cause between experimental arms and the 7+3 arm will be reported for each arm every data and safety monitoring committee (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.

Time to count recovery

Time frame: After cycle 1 and cycle 2

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.

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

Will be estimated using the Kaplan-Meier method.

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

Defined for only patients achieving CR, or CRi. Will be estimated using the Kaplan-Meier method.

Overall survival

Time frame: From day of randomization on study until death from any cause, assessed up to 5 years

Will be estimated using the Kaplan-Meier method.

Time to relapse

Time frame: Up to 5 years

Will be estimated with cumulative incidence curves with death without relapse analyzed a competing event. Response per 2017 European LeukemiaNet guidelines will be tabulated and exact 95% confidence intervals will be calculated.

MRD negative complete remission (MRDneg CR)

Time frame: Up to 5 years

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.

Incidence of adverse events

Time frame: Up to 5 years

Will be analyzed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0

No results are flagged as posted.

Review the complete result tables and limitations in the official record.

Open official results ↗

Research locations (227)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

Find a location in this study

227 locations

University of Alabama at Birmingham Cancer CenterBirmingham, Alabama, United StatesRecruiting

Site Public ContactCONTACTgingerreeves@uabmc.edu

Razan MohtyPRINCIPAL_INVESTIGATOR

What this study involves

About the research

Who may be able to participate?

Treatment, groups and participation

What researchers are measuring

Primary measures

Secondary measures

Research locations (227)

Study team and timeline

Official study contacts

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