NCT05554419

Brief Summary

This phase II MyeloMATCH treatment trial compares cytarabine versus (vs.) cytarabine and venetoclax vs. liposome-encapsulated daunorubicin-cytarabine and venetoclax vs. azacitidine and venetoclax for treating patients who have residual disease after treatment for acute myeloid leukemia (AML). Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. 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. Liposome-encapsulated daunorubicin-cytarabine is a drug formulation that delivers daunorubicin and cytarabine in small spheres called liposomes, which may make the drugs safer or more effective. Azacitidine is a drug that interacts with DNA and leads to the activation of tumor suppressor genes, which are genes that help control cell growth. This study may help the study doctors find out if the different drug combinations are equally effective to the usual approach of cytarabine alone while requiring a shorter duration of treatment. To decide if they are better, the study doctors will be looking to see if the study drugs lead to a higher percentage of patients achieving a deeper remission compared to cytarabine alone.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
184

participants targeted

Target at P75+ for phase_2

Timeline
2mo left

Started Jul 2026

Shorter than P25 for phase_2

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 23, 2022

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 26, 2022

Completed
3.8 years until next milestone

Study Start

First participant enrolled

July 1, 2026

Expected
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2026

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2026

Last Updated

April 13, 2026

Status Verified

February 1, 2026

Enrollment Period

2 months

First QC Date

September 23, 2022

Last Update Submit

April 9, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Frequency of measurable residual disease (MRD) negative complete remission (CR)

    Will be centrally evaluated. The MRD negative CR frequency will be compared between each experimental arm and the standard therapy arm using Fisher's exact test with one-sided alpha of 0.10 for each comparison. Test results with one-sided p-value \< 0.10 will be considered statistically significant. Multivariable logistic regression modeling will also be used to examine the treatment effect between each experimental arm and the standard therapy arm, adjusting for stratification factors and other possible clinical and biological risk factors.

    Following 2 cycles of consolidation (56 days)

Secondary Outcomes (4)

  • Overall survival

    Between randomization and death from any cause, assessed up to 10 years

  • Disease-free survival

    From randomization to relapse or death in remission, assessed up to 10 years

  • Rate of allogeneic transplant

    Up to 10 years

  • Incidence of adverse events

    Up to 10 years

Study Arms (4)

ARM A (cytarabine)

ACTIVE COMPARATOR

Patients receive cytarabine IV on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.

Procedure: Bone Marrow Aspiration and BiopsyDrug: CytarabineProcedure: Echocardiography TestProcedure: Multigated Acquisition Scan

ARM B (cytarabine, venetoclax)

EXPERIMENTAL

Patients receive cytarabine IV and venetoclax PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.

Procedure: Bone Marrow Aspiration and BiopsyDrug: CytarabineProcedure: Echocardiography TestProcedure: Multigated Acquisition ScanDrug: Venetoclax

ARM C (liposomal daunorubicin-cytarabine, venetoclax)

EXPERIMENTAL

Patients receive liposome-encapsulated daunorubicin-cytarabine IV and venetoclax PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.

Procedure: Bone Marrow Aspiration and BiopsyProcedure: Echocardiography TestDrug: Liposome-encapsulated Daunorubicin-CytarabineProcedure: Multigated Acquisition ScanDrug: Venetoclax

ARM D (azacitidine, venetoclax)

EXPERIMENTAL

Patients receive azacitidine IV or SC and venetoclax PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or MUGA as clinically indicated.

Drug: AzacitidineProcedure: Bone Marrow Aspiration and BiopsyProcedure: Echocardiography TestProcedure: Multigated Acquisition ScanDrug: Venetoclax

Interventions

Given IV

Also known as: CPX 351, CPX-351, CPX351, Cytarabine and Daunorubicin Liposomal, Cytarabine-Daunorubicin Liposome for Injection, Daunorubicin and Cytarabine (Liposomal), Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos
ARM C (liposomal daunorubicin-cytarabine, venetoclax)

Undergo MUGA

Also known as: 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
ARM A (cytarabine)ARM B (cytarabine, venetoclax)ARM C (liposomal daunorubicin-cytarabine, venetoclax)ARM D (azacitidine, venetoclax)

Given IV

Also known as: .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
ARM A (cytarabine)ARM B (cytarabine, venetoclax)

Undergo ECHO

Also known as: EC, Echocardiography
ARM A (cytarabine)ARM B (cytarabine, venetoclax)ARM C (liposomal daunorubicin-cytarabine, venetoclax)ARM D (azacitidine, venetoclax)

Given PO

Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto
ARM B (cytarabine, venetoclax)ARM C (liposomal daunorubicin-cytarabine, venetoclax)ARM D (azacitidine, venetoclax)

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza
ARM D (azacitidine, venetoclax)

Undergo bone marrow aspiration and biopsy

ARM A (cytarabine)ARM B (cytarabine, venetoclax)ARM C (liposomal daunorubicin-cytarabine, venetoclax)ARM D (azacitidine, venetoclax)

Eligibility Criteria

Age18 Years - 59 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Patient must be \>= 18 and =\< 59 years of age
  • Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patient must have morphologically documented AML or secondary AML (from prior conditions such as myelodysplastic syndrome \[MDS\], myeloproliferative neoplasm \[MPN\]) or therapy related AML (t-AML), as defined by World Health Organization (WHO) criteria
  • Patient must have completed induction chemotherapy in a myeloMATCH young adult tier-1 protocol. Patient may have received prior hypomethylating agents (HMAs). Patient may have received prior azacitidine + venetoclax
  • Patient must have been assigned to this protocol by myeloMATCH master screening and reassessment protocol (MSRP)/MATCHBOX. Patients thereby assigned will have attained complete remission (CR) or CR with partial hematologic recovery (CRh) (defined as CR with \[absolute neutrophil count (ANC)\] \>= 500/mcL and/or platelets \> 50/mcL) with detectable MRD at time of assignment. MRD is defined as \> 0.1% flow cytometry on bone marrow (BM) biopsy as assessed by MDNet. The definition of CR or CRh may be made +/- 2 weeks from BM biopsy
  • 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
  • Patient must have recovered (i.e.: resolved to \< grade 2) from adverse events related to prior anti-cancer therapy at the time of randomization with the exception of alopecia
  • Absolute neutrophil count (ANC) \>= 500/mcL (obtained =\< 7 days prior to protocol randomization)
  • Platelets \>= 50,000/mcL (obtained =\< 7 days prior to protocol randomization)
  • Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (obtained =\< 7 days prior to protocol randomization)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN (obtained =\< 7 days prior to protocol randomization)
  • Creatinine =\< 1.5 x institutional ULN OR \>= 50 mL/min.1.73 m\^2 (obtained =\< 7 days prior to protocol randomization)
  • 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
  • +3 more criteria

You may not qualify if:

  • 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 sexual orientation or 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)
  • Patients of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and continue for 6 months after the last dose of daunorubicin + cytarabine liposome, 6 months after the last dose of azacitidine for patients of childbearing potential, 3 months after the last dose of azacitidine for male patients, and for 30 days after the last dose of venetoclax. Patient must also abstain from nursing an infant for 2 weeks after the last dose of daunorubicin + cytarabine liposome and for 1 week after the last dose of azacitidine
  • Patients must not have FLT3 TKD or ITD mutation. Patients with this mutation, will be excluded from this study because myeloMATCH plans separate studies in tier-2 for those patients
  • Patient must not be receiving any other investigational agents at the time of randomization
  • Patient must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to cytarabine, azacitidine, venetoclax or daunorubicin and cytarabine liposome
  • Patients must not have uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or serious chronic gastrointestinal conditions associated with diarrhea

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

AzacitidineBiopsyCytarabineCPX-351DaunorubicinInjectionsLiposomesvenetoclax

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesCytodiagnosisCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisSpecimen HandlingDiagnostic Techniques, SurgicalSurgical Procedures, OperativeInvestigative TechniquesArabinonucleosidesAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesDrug Administration RoutesDrug TherapyTherapeuticsMembranes, ArtificialBiomedical and Dental MaterialsDrug CarriersDosage FormsPharmaceutical PreparationsManufactured MaterialsTechnology, Industry, and AgricultureBiomimetic Materials

Study Officials

  • Ehab L Atallah

    ECOG-ACRIN Cancer Research Group

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 23, 2022

First Posted

September 26, 2022

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

August 31, 2026

Last Updated

April 13, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will share

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.

More information