Induction and Consolidation With Fludarabine, Cytarabine, Idarubicin, and Venetoclax for the Treatment of Acute Myeloid Leukemia

NCT07228273 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: STUDY00028170NCI-2025-04104
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial compares induction and consolidation therapy with fludarabine, cytarabine, idarubicin, and venetoclax to cytarabine and daunorubicin induction and cytarabine consolidation for the treatment of acute myeloid leukemia (AML). Patients with AML often receive induction and consolidation therapy. Induction therapy is given first to get the patient's AML under control (remission). Consolidation therapy is given after the cancer has disappeared following the initial therapy. Consolidation therapy is used to kill any cancer cells that may be left in the body. Chemotherapy drugs, such as fludarabine, cytarabine, idarubicin, 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. 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. Giving fludarabine, cytarabine, idarubicin, and venetoclax for induction and consolidation therapy may be more effective in treating AML.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Percentage of participants achieving measurable residual disease negative composite complete remission (CRc-MRD-)

  Will be defined as the achievement of both measurable disease negative (MRD-) by multiparameter flow cytometry and complete response (CR), CR with partial hematologic recovery (CRh), or CR with incomplete blood count recovery (CRi). Participants who do not qualify as efficacy-evaluable (usually due to early death or withdrawal because of toxicity) will be considered non-responders. A point estimate and 95% exact confidence interval (CI) for CRc MRD- will be computed for each arm (and time point) separately and the CRc MRD- rate will be statistically compared across arms with Fisher's exact test at 3 timepoints: end of induction, end of the first consolidation cycle, and end of treatment. A Hochberg multiplicity adjustment will be applied to the p-values from these 3 Fisher exact tests to control the family wise error rate (at α=0.05) for between-arm comparisons of the primary endpoint. CRc MRD- status at each of the above-specified time points will be modeled with logistic regression.

  Up to 30 days post last dose of study drug

Secondary Outcomes (15)

• Percentage of participants achieving CR

  Up to 30 days post last dose of study drug

• Percentage of participants achieving composite complete remission (CRc)

  Up to 30 days post last dose of study drug

• Percentage of participants achieving an overall response (ORR)

  Up to 30 days post last dose of study drug

• Incidence of treatment-emergent grade ≥ 3 adverse events (AEs)

  Up to 30 days after the last dose of any study drug

• Event free survival (EFS)

  From cycle (C)1 day(D)1 to first occurrence of treatment failure, disease progression, or death due to any cause, assessed up to 2 years

Study Arms (2)

Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax)

EXPERIMENTAL

See Detailed Description.

Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Procedure: Echocardiography Test; Drug: Fludarabine; Drug: Idarubicin; Procedure: Multigated Acquisition Scan; Other: Questionnaire Administration; Drug: Venetoclax

Arm 2 (cytarabine, daunorubicin)

ACTIVE COMPARATOR

INDUCTION: Patients receive cytarabine IV on days 1-7 and daunorubicin IV on days 1-3 of each cycle. Cycles repeat every 28 days for up to 1 cycle in the absence of disease progression or unacceptable toxicity. Patients achieving CR, CRh, CRi, or MLFS after one induction cycle proceed to consolidation. Patients achieving PR after one induction cycle may proceed to consolidation at the investigator's discretion. Patients with ≥ 5% blasts after one induction cycle may receive a second cycle of induction therapy. CONSOLIDATION: Participants receive cytarabine IV over 3 hours BID on days 1, 3, and 5 of each cycle. Cycles repeat every 28 days for up to 4 post-induction cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo ECHO or MUGA scan during screening and on study as clinically indicated. Patients also undergo bone marrow aspiration and biopsy and blood sample collection throughout the trial.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Drug: Daunorubicin; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm 2 (cytarabine, daunorubicin)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax); Arm 2 (cytarabine, daunorubicin)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax); Arm 2 (cytarabine, daunorubicin)

Cytarabine DRUG

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 1 (fludarabine, cytarabine, idarubicin, venetoclax); Arm 2 (cytarabine, daunorubicin)

Daunorubicin DRUG

Given IV

Also known as: Daunomycin, Daunorrubicina, DNR, Leukaemomycin C, Rubidomycin, Rubomycin C

Arm 2 (cytarabine, daunorubicin)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax); Arm 2 (cytarabine, daunorubicin)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax)

Idarubicin DRUG

Given IV

Also known as: 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDR

Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

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 1 (fludarabine, cytarabine, idarubicin, venetoclax); Arm 2 (cytarabine, daunorubicin)

Questionnaire Administration OTHER

Ancillary studies

Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax); Arm 2 (cytarabine, daunorubicin)

Venetoclax DRUG

Given PO

Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto

Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to comprehend the investigational nature of the study and provide written informed consent
• Age 18 to ≤ 65 years (yrs), at the time of consent
• All gender identities, races, or ethnicities are eligible
• Newly documented, previously untreated diagnosis of AML or myelodysplastic syndrome (MDS) with marrow blasts ≥ 10%, in agreement with 2022 European LeukemiaNet criteria (ELN22)
• Leukapheresis and treatment with cytarabine or hydroxyurea prior to study initiation is permitted for cytoreduction in patients with proliferative disease. NOTE: Treatment with cytarabine is limited to up to 2 grams total at least 14 days prior to starting on protocol defined therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Willingness to undergo hematopoietic stem cell transplant (HSCT)
• Ability to take medications by mouth or feeding tube
• Adequate hematologic and organ function
• Institutional standards, New York Heart Association (NYHA) criteria for cardiac function
• Calculated creatinine clearance (according to the Cockcroft-Gault equation) \> 40 mL/min
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 3 x upper limit of normal (ULN), unless considered due to leukemic involvement
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x ULN, unless considered due to leukemic involvement
• Total bilirubin ≤ 1.5 x ULN, unless due to Gilbert's disease or leukemic involvement
• Willing and able to

You may not qualify if:

• Documented t(15;17) (acute promyelocytic leukemia \[APL\]), and/or mutation(s) to FLT3 ITD or core binding factor (CBF). Point mutations within the tyrosine kinase domain (FLT3 TKD) are allowed
• Another active malignancy within the previous 5 years, except treated early stage carcinomas of the skin, or at the investigator's discretion
• Known, active central nervous system (CNS) involvement with AML
• Recent and significant medical interventions, such as major surgery within 28 days of start of treatment
• GVHD or autologous stem cell transplant within 100 days of start of treatment
• Currently receiving investigational therapy or chemotherapy within 28 days, or 5 half-lives, whichever is longer, with the exception of hydroxyurea or cytarabine for cytoreduction purposes
• Prior treatment with a BCL 2 inhibitor within 12 months prior to the start of treatment
• Use of strong or moderate CYP3A4 inducers or inhibitors or P-gp inhibitors within 2 days or 3 half-lives, whichever is longer, prior to start of treatment with venetoclax or at the discretion of the investigator if dose reductions, based on the interaction, have been specified
• History of allergic response to any of the interventional agents or any excipients in the formulations
• Inadequate organ function, including the following (or at the discretion of the investigator):
• History of New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) \< 40% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
• Unstable/uncontrolled angina pectoris, history of severe and/or uncontrolled ventricular arrhythmias, or history of myocardial infarction within the last 6 months
• A white blood cell count (WBC) \> 25 x 10\^⁹/L
• Known dysphagia in the absence of a feeding tube, short-gut syndrome, or other conditions or causes that would affect the ingestion and/or gastrointestinal absorption of drugs administered orally
• Active hepatic disorder or documented positive hepatitis B or C virus (HBV/HCV, respectively) status, except in cases of undetectable HBV/HCV viral load for at least 3 months prior to the start of treatment. (Hepatitis B or C testing is not required for eligibility assessment.)

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Specimen Handling; Biopsy; Cytarabine; Daunorubicin; fludarabine; Idarubicin; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Curtis A Lachowiez

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 12, 2025
• First Posted: November 14, 2025
• Study Start: December 12, 2025
• Primary Completion (Estimated): June 24, 2029
• Study Completion (Estimated): August 24, 2029
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (1)