Acute Myeloid Leukemia Clinical Trial

Testing the Effects of Novel Therapeutics for Newly Diagnosed, Untreated Patients With High-Risk Acute Myeloid Leukemia (A MyeloMATCH Treatment 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.

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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.

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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

STEP 1 REGISTRATION:

Participants must have been registered to Master Screening and Re-Assessment Protocol, myeloMATCH MSRP, 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 MSRP
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 is for people with:

Acute Myeloid Leukemia

Phase:

Phase 2

Estimated Enrollment:

335

Study ID:

NCT05554406

Recruitment Status:

Recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 12 Locations for this study

See Locations Near You

Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor Michigan, 48106, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Tareq Al Baghdadi
Principal Investigator
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton Michigan, 48114, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Tareq Al Baghdadi
Principal Investigator
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton Michigan, 48188, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Tareq Al Baghdadi
Principal Investigator
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea Michigan, 48118, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Tareq Al Baghdadi
Principal Investigator
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia Michigan, 48154, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Tareq Al Baghdadi
Principal Investigator
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti Michigan, 48197, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Tareq Al Baghdadi
Principal Investigator
Siteman Cancer Center at West County Hospital
Creve Coeur Missouri, 63141, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Ramzi Abboud
Principal Investigator
Washington University School of Medicine
Saint Louis Missouri, 63110, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Ramzi Abboud
Principal Investigator
Siteman Cancer Center-South County
Saint Louis Missouri, 63129, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Ramzi Abboud
Principal Investigator
Siteman Cancer Center at Christian Hospital
Saint Louis Missouri, 63136, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Ramzi Abboud
Principal Investigator
Siteman Cancer Center at Saint Peters Hospital
Saint Peters Missouri, 63376, United States More Info
Site Public Contact
Contact
800-600-3606
[email protected]
Ramzi Abboud
Principal Investigator
SWOG
Portland Oregon, 97239, United States More Info
Paul J. Shami
Contact
[email protected]
Paul J. Shami
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 2

Estimated Enrollment:

335

Study ID:

NCT05554406

Recruitment Status:

Recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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