Testing the Addition of Venetoclax or Gemtuzumab Ozogamicin (GO) to Usual Treatment Regimen (Cytarabine and Daunorubicin, "7+3") for Core Binding Factor Acute Myeloid Leukemia (CBF-AML) to Improve Response (A MyeloMATCH Treatment Trial)

NCT ID: NCT06917911

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

162 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-18

Study Completion Date

2027-11-25

Brief Summary

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This phase II MyeloMATCH treatment trial compares the effect of venetoclax to gemtuzumab ozogamicin, when given with cytarabine and daunorubicin ("7+3" regimen), for the treatment of patients with core binding factor acute myeloid leukemia (CBF-AML). 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. Gemtuzumab ozogamicin is a monoclonal antibody, called gemtuzumab, linked to an antitumor antibiotic drug, called ozogamicin. Gemtuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD33 receptors, and delivers ozogamicin to kill them. 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 venetoclax with cytarabine and daunorubicin may have fewer side effects and be as effective or better than the combination with gemtuzumab ozogamicin in treating patients with core binding factor AML.

Detailed Description

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PRIMARY OBJECTIVE:

I. Compare the rates of complete remission (CR) without measurable residual disease (CRMRD-) by multiparameter flow cytometry following induction therapy between the two treatment arms in each cohort separately.

SECONDARY OBJECTIVES:

I. To compare the rates of CR and composite complete remission (CRc) (CR+complete remission with incomplete hematologic recovery \[CRi\]+complete remission with partial hematologic recovery \[CRh\]) between the treatment arms.

II. To compare the overall survival (OS) between the treatment arms. III. To compare the event-free survival (EFS). IV. To compare cumulative incidence of relapse (CIR). V. To compare cumulative incidence of death (CID) between the treatment arms. VI. To compare the rate of early death at 30 days and 60 days between the treatment arms.

VII. To assess the rate and frequency of adverse events between treatment arms. VIII. To evaluate mutant RAS and mutant KIT as predictive biomarkers for CRMRD- rate in CBF AML.

EXPLORATORY OBJECTIVE:

I. To compare MRD (and its clinical implication, e.g., relapse rates) between flow cytometry (FC) and next generation sequencing (NGS)-based (RUNX1::RUNX1T1 or CBFB::MYH11).

CORRELATIVE OBJECTIVES:

I. To evaluate the frequency and clinical impact of variant allele frequency (VAF) of KIT mutation, KIT mutations in different exons (e.g., exon 8 or 17), CD33 expression, additional (secondary) mutations and cytogenetic abnormalities.

II. To evaluate the differences in clinical and molecular outcomes in patients with RUNX1::RUNX1T1 mutated versus CBFB::MYH11 mutated CBF AML.

OUTLINE: Patients are randomized to 1 of 2 regimens.

REGIMEN 1: Patients receive gemtuzumab ozogamicin intravenously (IV) on days 1 and 4, cytarabine IV, continuously, on days 1-7 and daunorubicin IV on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care consolidation/post-remission treatment at the discretion of the treating physician. Patients undergo echocardiography or multigated acquisition (MUGA) scan during screening and bone marrow aspiration and biopsy and blood sample collection throughout the study. Patients may also undergo optional buccal swab collection throughout the study.

REGIMEN 2: Patients receive venetoclax orally (PO) once daily (QD) on days 1-11, cytarabine IV, continuously, on days 2-8 and daunorubicin IV on days 2-4 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care consolidation/post-remission treatment at the discretion of the treating physician. Patients undergo echocardiography or MUGA scan during screening and bone marrow aspiration and biopsy and blood sample collection throughout the study. Patients may also undergo optional buccal swab collection throughout the study.

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

Conditions

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Core Binding Factor Acute Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Regimen 1 (gemtuzumab ozogamicin 7+3)

Patients receive gemtuzumab ozogamicin IV on days 1 and 4, cytarabine IV, continuously, on days 1-7 and daunorubicin IV on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care consolidation/post-remission treatment at the discretion of the treating physician. Patients undergo echocardiography or MUGA scan during screening and bone marrow aspiration and biopsy and blood sample collection throughout the study. Patients may also undergo optional buccal swab collection throughout the study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo optional buccal cell collection and/or blood sample collection

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Cytarabine

Intervention Type DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type DRUG

Given IV

Echocardiography Test

Intervention Type PROCEDURE

Undergo echocardiography

Gemtuzumab Ozogamicin

Intervention Type DRUG

Given IV

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA scan

Regimen 2 (Venetoclax, 7+3)

Patients receive venetoclax orally (PO) once daily (QD) on days 1-11, cytarabine IV, continuously, on days 2-8 and daunorubicin IV on days 2-4 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care consolidation/post-remission treatment at the discretion of the treating physician. Patients undergo echocardiography or MUGA scan during screening and bone marrow aspiration and biopsy and blood sample collection throughout the study. Patients may also undergo optional buccal swab collection throughout the study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo optional buccal cell collection and/or blood sample collection

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow aspiration

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Cytarabine

Intervention Type DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type DRUG

Given IV

Echocardiography Test

Intervention Type PROCEDURE

Undergo echocardiography

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA scan

Venetoclax

Intervention Type DRUG

Given PO

Interventions

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Biospecimen Collection

Undergo optional buccal cell collection and/or blood sample collection

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type PROCEDURE

Cytarabine

Given IV

Intervention Type DRUG

Daunorubicin Hydrochloride

Given IV

Intervention Type DRUG

Echocardiography Test

Undergo echocardiography

Intervention Type PROCEDURE

Gemtuzumab Ozogamicin

Given IV

Intervention Type DRUG

Multigated Acquisition Scan

Undergo MUGA scan

Intervention Type PROCEDURE

Venetoclax

Given PO

Intervention Type DRUG

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Biopsy of Bone Marrow Biopsy, Bone Marrow .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 1-Beta-D-arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-Cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HCl Daunorubicini Hydrochloridum FI-6339 Ondena RP-13057 Rubidomycin Hydrochloride Rubilem EC Echocardiography Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody CDP-771 CMA-676 gemtuzumab hP67.6-Calicheamicin Mylotarg WAY-CMA-676 Blood Pool Scan Equilibrium Radionuclide Angiography Gated Blood Pool Imaging Gated Heart Pool Scan MUGA MUGA Scan Multi-Gated Acquisition Scan Radionuclide Ventriculogram Scan Radionuclide Ventriculography RNV Scan RNVG SYMA Scanning Synchronized Multigated Acquisition Scanning ABT 199 ABT-0199 ABT-199 ABT199 GDC 0199 GDC-0199 GDC0199 RG7601 Venclexta Venclyxto

Eligibility Criteria

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Inclusion Criteria

* GENERAL MYELOMATCH CRITERIA: Patients must be registered to the Master Screening and Reassessment Protocol and assigned to this protocol by the MATCHBox Treatment Verification Team
* GENERAL MYELOMATCH CRITERIA: Participants must not have received prior anti-cancer therapy for AML or myelodysplastic syndrome (MDS)

* Note: Hydroxyurea to control the white blood cell count (WBC) and cytarabine up to 1 g/m\^2 for urgent cytoreduction is allowed.
* Note: Prior erythroid stimulating agent (ESA) is not considered prior therapy for the purposes of eligibility
* GENERAL MYELOMATCH CRITERIA: Participants must not receive any cytarabine-containing therapy other than up to 1 g/m\^2 of cytarabine, which is allowed for urgent cytoreduction. The use of prior hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide is allowed
* Diagnosis of AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 or AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11. No FLT3 mutation (these patients should be considered for a FLT3-focused Myelomatch study)
* No prior AML or MDS-directed therapy except for urgent treatment of leukocytosis with leukapheresis, cytarabine, and hydroxyurea, Prior intrathecal chemotherapy for central nervous system (CNS) involvement of AML is permitted
* Age 18-59 years
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless patient has a history of Gilbert syndrome and direct bilirubin is ≤ 1.5 x ULN)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x upper limit of normal (ULN)
* Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73m\^2
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done ≤ 7 days prior to registration is required
* 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
* Participants with CNS disease are eligible for this trial and will be treated according to institutional guidelines with intrathecal chemotherapy for this aspect of their disease
* Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration 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 known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* No known medical condition causing an inability to swallow oral formulations of agents
Minimum Eligible Age

18 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Celalettin Ustun

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Other Identifiers

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NCI-2025-02426

Identifier Type: REGISTRY

Identifier Source: secondary_id

MM1YA-A04

Identifier Type: OTHER

Identifier Source: secondary_id

MM1YA-A04

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2025-02426

Identifier Type: -

Identifier Source: org_study_id