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

NCT ID: NCT07228273

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-12
• Study Completion Date: 2029-08-24

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.

Detailed Description

PRIMARY OBJECTIVE:

I. Assess the efficacy of treatment based on rates of measurable residual disease negative composite complete remission (CRc-MRD-) determined using multiparameter flow cytometry (MFC).

SECONDARY OBJECTIVES:

I. Assess the efficacy of treatment based on complete response (CR) disease remission.

II. Assess the efficacy of treatment based on overall clinical response. III. Assess the safety of treatment. IV. Assess survival in the absence of treatment failure, hematologic relapse, or progressive disease.

V. Assess patient survival after commencing study therapy. VI. Assess the delay in hematopoietic stem cell transplant (HSCT) referral and consultation for transition to HSCT.

VII. Assess the efficacy of treatment based on transitioning to HSCT. VIII. Assess disease response after transplant among participants who proceed to HSCT.

IX. Assess risk of post-transplant infection among participants who proceed to HSCT.

X. Assess risk of post-transplant graft versus host disease (GVHD) among participants who proceed to HSCT.

XI. Assess survival in the absence of post-HSCT GVHD and relapse among participants who proceed to HSCT.

EXPLORATORY OBJECTIVES:

I. Evaluate the depth of response with measurable residual disease (MRD) testing and compare methods of determining MRD status.

II. Evaluate survival of measurable residual disease negative (MRD-) patients with CR versus CR with partial or incomplete hematologic recovery.

III. Assess participant quality of life (QoL) using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1:

INDUCTION: Patients receive fludarabine intravenously (IV) over 30 minutes and cytarabine IV over 4 hours on days 2, 3, 4, 5, and 6, idarubicin IV over 15-30 minutes on days 4, 5, and 6, and venetoclax orally (PO) once daily (QD) on days 3-9 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, CR with partial hematologic recovery (CRh), CR with incomplete blood count recovery (CRi), or morphologic leukemia-free state (MLFS) after one induction cycle proceed to consolidation. Patients achieving partial response (PR) after one induction cycle may proceed to consolidation at the investigator's discretion. Patients with ≥ 5% blasts after one cycle of induction may receive a second cycle of induction therapy.

CONSOLIDATION: Patients receive fludarabine IV over 30 minutes and cytarabine IV over 4 hours on days 2, 3, and 4 of each cycle, idarubicin IV over 15-30 minutes on days 4, 5, and 6 of either cycles 3 and 6 or cycles 4 and 7, and venetoclax PO QD on days 3-9 of each cycle. Cycles repeat every 28 days for up to 6 post-induction cycles in the absence of disease progression or unacceptable toxicity.

ARM 2:

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 twice daily (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, all patients undergo echocardiography (ECHO) or multigated acquisition (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.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax)

See Detailed Description.

Group Type: EXPERIMENTAL

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

Echocardiography Test

Intervention Type: PROCEDURE

Undergo ECHO

Fludarabine

Intervention Type: DRUG

Given IV

Idarubicin

Intervention Type: DRUG

Given IV

Multigated Acquisition Scan

Intervention Type: PROCEDURE

Undergo MUGA scan

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Venetoclax

Intervention Type: DRUG

Given PO

Arm 2 (cytarabine, daunorubicin)

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.

Group Type: ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo 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

Intervention Type: DRUG

Given IV

Echocardiography Test

Intervention Type: PROCEDURE

Undergo ECHO

Multigated Acquisition Scan

Intervention Type: PROCEDURE

Undergo MUGA scan

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Interventions

Biospecimen Collection

Undergo 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

Given IV

Intervention Type: DRUG

Echocardiography Test

Undergo ECHO

Intervention Type: PROCEDURE

Fludarabine

Given IV

Intervention Type: DRUG

Idarubicin

Given IV

Intervention Type: DRUG

Multigated Acquisition Scan

Undergo MUGA scan

Intervention Type: PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Venetoclax

Given PO

Intervention Type: DRUG

Other Intervention Names

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; Daunomycin; Daunorrubicina; DNR; Leukaemomycin C; Rubidomycin; Rubomycin C; EC; Echocardiography; Fluradosa; 4-Demethoxydaunomycin; 4-Demethoxydaunorubicin; 4-DMDR; 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

Inclusion Criteria

• 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

• Adhere to study schedule of activities and lifestyle restrictions while on treatment;
• Provide bone marrow (BM) aspirate and core biopsy samples; AND
• Accept supportive and prophylactic care for hematologic toxicities, infection, and immediate sequelae, including transfusions
• Negative pregnancy test within 3 days of start of treatment for persons of childbearing potential (PCBP)
• Based on animal studies and the known pharmacology of the study drugs, PCBP and sperm-producing participants who are sexually active with a PCBP must comply with study requirements for contraception

• PCBP (participants and PCBP partners of participants) must agree to use an approved contraception and to refrain from donating / cryopreserving ova from cycle (C) 1 day (D) 1 until 6 months following the last dose of study treatment
• Participants who produce viable sperm and who have intercourse with PCBP must agree to use an approved contraception method and to refrain from donating sperm from C1D1 until 3 months following the last dose of study treatment

Exclusion Criteria

• 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.)
• Individuals with positive serology for human immunodeficiency virus (HIV) who are undergoing treatment with highly active antiretroviral therapy (HAART) (or another therapy that may interfere with metabolism of study agents) are not eligible. If the HIV infection is controlled with another medication type or if an acceptable alternative HIV treatment can be substituted for HAART, enrollment may proceed
• Uncontrolled infection. Participants with controlled infection must be afebrile and hemodynamically stable for at least 72 hours prior to start of treatment and must be amenable to alternate treatment if current treatment will interact with investigational regimen
• Psychiatric illness/social situations that would limit compliance with study requirements
• Unwillingness to stop breastfeeding. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding is not allowed throughout the study for 6 weeks after the last dose of study drug

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Curtis Lachowiez

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Curtis A Lachowiez

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Locations

OHSU Knight Cancer Institute

Portland, Oregon, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Curtis A. Lachowiez

Role: primary

lachowie@ohsu.edu

503-494-6157

Other Identifiers

NCI-2025-04104

Identifier Type: REGISTRY

Identifier Source: secondary_id

STUDY00028170

Identifier Type: OTHER

Identifier Source: secondary_id

STUDY00028170

Identifier Type: -

Identifier Source: org_study_id