AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 2NCT07862517

Testing the Investigational Medication Combination of Azacitidine, Venetoclax, and Quizartinib Compared to the Usual Treatment of Cytarabine, Daunorubicin, and Quizartinib for Patients With FLT3-ITD Mutant Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)

A Phase 2 study testing Azacitidine, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Myeloid Leukemia, run by National Cancer Institute (NCI).

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
Search all trials

Trial summary

This phase II MyeloMATCH treatment trial compares the combination of azacitidine, venetoclax and quizartinib to the standard treatment of cytarabine, daunorubicin and quizartinib for the treatment of patients with FLT3-ITD mutant acute myeloid leukemia. Read more about this study

Who is it for?
Ages 18 to 59 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Azacitidine, Biospecimen Collection and Bone Marrow Aspiration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
122 participants
Where
No sites listed yet
Study dates
15 Jan 2027to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 59 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Patient must be ≥ 18 and ≤ 59 years of age
  • Patient must be assigned to this protocol by the MYELOMATCH Protocol
  • Patient must have newly diagnosed acute myeloid leukemia (AML) with FLT3 ITD mutation as assessed by central myeloMATCH testing with variant allele frequency (VAF) over 5%
  • Patient must not have any contraindications to the conventional chemotherapy used in this study
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Patient must not have Core-binding factor [inv(16), t(16;16) or t(8;21)] leukemia
Show all 39Show fewer
  • Patient must not have acute promyelocytic leukemia
  • Patient must not have had prior therapy with deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) for myelodysplastic syndrome (MDS)
  • Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Contraception measures must continue for:
  • 7 months after the last dose of quizartinib for patients of childbearing potential and for 4 months after the last dose of quizartinib for patients who are able to father children
  • 6 months after the last dose of daunorubicin for all patients
  • 30 days after the last dose of venetoclax for patients of childbearing potential
  • 6 months after the last dose of azacitidine for patients of childbearing potential and for 4 months after the last dose of azacitidine for patients who are able to father children In addition, patient must not breastfeed during treatment and for 1 month after treatment ends
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • Total bilirubin ≤ 2 x institutional upper limit of normal (ULN). Patients with Gilbert's Syndrome must have total bilirubin ≤ 3 x institutional ULN (labs must be obtained ≤ 7 days prior to protocol randomization)
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3.0 × institutional ULN (labs must be obtained ≤ 7 days prior to protocol randomization)
  • Creatinine Clearance (CrCL) ≥ 30 mL/min calculated using the Cockcroft-Gault equation (labs must be obtained ≤ 7 days prior to protocol randomization)
  • Left ventricular ejection fraction > 45% (which must be obtained ≤ 2 weeks prior to randomization)
  • NOTE: Since quizartinib can increase corrected QT interval (QTc) and many patients will require supportive care agents that affect QTc, a baseline electrocardiogram (ECG) ≤ 2 weeks prior to randomization is recommended if clinically indicated
  • Patient must not have Common Terminology Criteria for Adverse Events (CTCAE) > grade 3 hypokalemia, hypomagnesemia, or hypocalcemia. Patients with grade 1-2 electrolyte abnormalities are eligible while electrolytes are being corrected
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients must not have had history of treatment with cardiotoxic agents unless total anthracycline lifetime dose is < 450 mg/m^2 doxorubicin equivalents
  • Patients must not have uncontrolled or significant cardiovascular disease, including any of the following:
  • Fridericia's formula-corrected QT (QTcF) interval > 450 ms;
  • Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome);
  • Systemic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg;
  • History of clinically relevant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);
  • History of second (Mobitz II) or third degree heart block (patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);
  • History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to randomization;
  • History of New York Heart Association class 3 or 4 heart failure;
  • Complete left bundle branch block
  • Patient must not require treatment with concomitant strong or moderate CYP3A4 inducers
  • Patient must not require treatment with concomitant strong CYP3A4 inhibitors (e.g., antifungal azoles) unless considered necessary for the prevention or treatment of infections - in which a quizartinib dose reduction will be required
  • Patient must not have any known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of quizartinib or venetoclax, including difficulty swallowing
  • Patient must not have any uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous

Who cannot join

None listed.

About this study

Official title: A Phase II Randomized Study of Induction Therapy Comparing Cytarabine, Daunorubicin, and Quizartinib vs Azacitidine, Venetoclax, and Quizartinib in FLT3-ITD Mutant Acute Myeloid Leukemia: A MyeloMATCH Substudy

This phase II MyeloMATCH treatment trial compares the combination of azacitidine, venetoclax and quizartinib to the standard treatment of cytarabine, daunorubicin and quizartinib for the treatment of patients with FLT3-ITD mutant acute myeloid leukemia. Azacitidine and quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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. Chemotherapy drugs, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving azacitidine, venetoclax and quizartinib may be more effective than giving cytarabine, daunorubicin and quizartinib for the treatment of patients with FLT3-ITD mutant acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine if measurable residual disease (MRD) negative complete response (CRMRD-) rate, as measured by multiparameter flow cytometry after 2 treatment cycles, for patients with FLT3-ITD mutated acute myeloid leukemia (AML) who receive azacitidine/venetoclax/quizartinib is non-inferior to those who receive quizartinib/cytarabine/daunorubicin during induction.

SECONDARY OBJECTIVES:

  1. To compare the MRD- composite complete response rate (CRc) (complete response [CR]+complete remission incomplete hematologic recovery [CRi]) in patients who receive azacitidine/venetoclax/quizartinib versus (vs) quizartinib/cytarabine/daunorubicin.

II. To compare the FLT3-ITD mutation undetectable CRc (CR+CRi) rate of patients with FLT3-ITD mutated AML who receive azacitidine/venetoclax/quizartinib to those who receive quizartinib/cytarabine/daunorubicin during induction as measured by Molecular Diagnostic Network (MDNet) next generation sequencing (NGS) assay.

III. To compare the transplantation rate of MRD- CRc (evaluated by flow cytometry) patients with FLT3-ITD mutated AML who receive azacitidine/venetoclax/quizartinib to those who receive quizartinib/cytarabine/daunorubicin during induction.

IV. To compare the CRc (CR+CRi) rate of patients with FLT3-ITD mutated AML who receive azacitidine/venetoclax/quizartinib vs quizartinib/cytarabine/daunorubicin.

  1. To compare the event free survival (EFS) of patients with FLT3-ITD mutated AML who receive azacitidine/venetoclax/quizartinib to those who receive quizartinib/cytarabine/daunorubicin and intermediate dose cytarabine/quizartinib during consolidation.

VI. To compare the overall survival (OS) of patients with FLT3-ITD mutated AML who receive azacitidine/venetoclax/quizartinib to those who receive quizartinib/cytarabine/daunorubicin during induction and intermediate dose cytarabine/quizartinib during consolidation.

VII. To compare the 30-day mortality of azacitidine/venetoclax/quizartinib to quizartinib/cytarabine/daunorubicin during induction and consolidation in this patient population.

VIII. To compare the toxicities of quizartinib plus standard therapy during induction and consolidation in this patient population in the form of total hospital days and total intensive care unit (ICU) days in cycle 1 and cycle 2 to the total hospital days and total ICU days in cycle 1 and cycle 2 azacitidine/venetoclax/quizartinib.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:

INDUCTION: Patients receive cytarabine intravenously (IV), over 24 hours, on days 1-7, daunorubicin IV on days 1-3, and quizartinib orally (PO) once daily (QD) on days 8-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo bone marrow aspiration/biopsy. Patients with ≥ 20% bone marrow cellularity and > 5% bone marrow leukemic blasts may repeat induction as described starting on day 28-45. Patients with ≥ 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts proceed to consolidation, following count recovery, by 30 days post-confirmation of CR/CRi. Patients with < 20% bone marrow cellularity and > 5% bone marrow leukemic blasts repeat the bone marrow aspiration/biopsy 1 week later and then either repeat induction or proceed to consolidation, based on results. Patients with < 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts proceed to consolidation.

CONSOLIDATION: Patients receive cytarabine IV, over 1-3 hours, every 12 hours on days 1, 3 and 5 and quizartinib PO QD on days 6-19 in the absence of disease progression or unacceptable toxicity.

ARM B:

CYCLE 1: Patients receive azacitidine IV or subcutaneously (SC) on days 1-7 or days 1-5 and 8-9, venetoclax PO QD on days 1-28, and quizartinib PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity and based on bone marrow findings. Patients undergo bone marrow aspiration/biopsy on day 14 of cycle 1. Patients with ≥ 20% bone marrow cellularity and > 5% bone marrow leukemic blasts continue treatment as described through day 28 of cycle 1 and then proceed to cycle 2 without interruption or delay, as long as repeat bone marrow aspiration/biopsy on day 28 of cycle 1 is consistent with persistent blasts > 5%. Patients with ≥ 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib for the remainder of the cycle (through day 28) and then proceed to cycle 2 of treatment as described following count recovery. Patients without count recovery by day 42 undergo repeat bone marrow aspiration/biopsy. Patients with count recovery by day 42 proceed to cycle 2 (by day 50). For patients without count recovery by day 50 whose repeat bone marrow aspiration/biopsy shows no blasts, initiation of cycle 2 will be discussed with the study chairs. Patients with < 20% bone marrow cellularity and > 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib, undergo repeat bone marrow aspiration/biopsy 1 week later, and proceed based on repeat biopsy results as described. Patients with < 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib for the remainder of the cycle (through day 28) and then proceed to cycle 2 of treatment as described following count recovery. Patients without count recovery by day 42 undergo repeat bone marrow aspiration/biopsy. Patients with count recovery by day 42 proceed to cycle 2 (by day 50). For patients without count recovery by day 50 whose repeat bone marrow aspiration/biopsy shows no blasts, initiation of cycle 2 will be discussed with the study chairs.

CYCLE 2: Patients receive azacitidine IV or SC on days 1-7 or days 1-5 and 8-9, venetoclax PO QD on days 1-28, and quizartinib PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity and based on bone marrow findings. Patients who do not achieve response after completion of cycle 1 undergo bone marrow aspiration/biopsy on day 14 of cycle 2. Patients with ≥ 20% bone marrow cellularity and > 5% bone marrow leukemic blasts continue venetoclax and quizartinib as described through day 28 of cycle 2. Patients with ≥ 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib for the remainder of the cycle (through day 28). Patients with < 20% bone marrow cellularity and > 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib, undergo repeat bone marrow aspiration/biopsy 1 week later, and proceed based on repeat aspiration/biopsy results as described. Patients with < 20% bone marrow cellularity and ≤ 5% bone marrow leukemic blasts interrupt venetoclax and quizartinib for the remainder of the cycle (through day 28).

Upon completion of two cycles of therapy on either Arm A or Arm B, patients who are eligible can proceed to allogeneic stem cell transplant; while awaiting allogeneic stem cell transplant, patients should continue standard of care therapy.

Patients undergo echocardiography or multigated acquisition (MUGA) scan during screening and undergo bone marrow aspiration and biopsy as well as blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for years 2-5.

Being tested
Azacitidine, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Cytarabine
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine

    Given IV or SC

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV

  • DaunorubicinDrug

    Also called Daunomycin, Daunorrubicina, DNR, Leukaemomycin C

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo echocardiography

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA scan

  • QuizartinibDrug

    Also called AC 220, AC-220, AC010220, AC220

    Given PO

  • VenetoclaxDrug

    Also called ABT 199, ABT-0199, ABT-199, ABT199

    Given PO

Study groups in NCT07862517
Study groupRoleWhat they receive
Arm A (cytarabine, daunorubicin, quizartinib)ExperimentalSee Detailed Description.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Drug: Daunorubicin; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Drug: Quizartinib
Arm B (azacitidine, venetoclax, quizartinib)ExperimentalSee Detailed Description.
Receives: Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Drug: Quizartinib; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of measurable residual disease (MRD) negative complete response (CR)

    As measured by multiparameter flow cytometry.

    Measured: After completion of 2 treatment cycles (cycle length = 28 days)

Secondary outcomes (7)

  1. Rate of MRD negative CR/complete remission incomplete hematologic recovery (CRi)

    Measured: Up to 5 years

  2. MRD negative CR

    Measured by Molecular Diagnostic Network next generation sequencing assay.

    Measured: Up to 5 years

  3. MRD negative composite complete response

    Measured: Up to 5 years

  4. Event free survival

    Will be calculated using the Kaplan-Meier method.

    Measured: From randomization to failure to achieve CR/CRi, or to relapse after CR/CRi or to death in remission, assessed up to 5 years

  5. Overall survival

    Will be calculated using the Kaplan-Meier method.

    Measured: From randomization to death, assessed up to 5 years

  6. 30-day mortality rate

    Will be compared between the treatment arms using Fisher's exact test.

    Measured: At 30 days

  7. Incidence of adverse events

    Will be determined using the Common Terminology Criteria for Adverse Events.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Oct 2026
  2. Study start15 Jan 2027 (estimated)
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
122 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07862517
Sponsor's protocol ID
NCI-2026-07106
Other IDs
NCI-2026-07106, MM1YA-EA05, MM1YA-EA05, U10CA180820
Status last verified
Oct 2026
First submitted
5 Oct 2026
Last updated
7 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Azacitidine, Biospecimen Collection and Bone Marrow Aspiration in people with Acute Myeloid Leukemia, run by National Cancer Institute (NCI).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 39 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of measurable residual disease (MRD) negative complete response (CR) (time frame: After completion of 2 treatment cycles (cycle length = 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07862517.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in