Recruiting
Phase 2

Fludarabine, Cytarabine, Idarubicin, Venetoclax vs. Cytarabine, Daunorubicin

Sponsor:

OHSU Knight Cancer Institute

Code:

NCT07228273

Conditions

Acute Myeloid Leukemia

Myelodysplastic Syndrome

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Cytarabine

Daunorubicin

Study Details

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

Study ID

NCT07228273

Start date

Dec 12, 2025

Status verified date

Jul, 2026

Completion date

Aug 24, 2029

Anticipated

Primary completion date

Jun 24, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

102 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax)

See Detailed Description.

active comparator: 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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Bone Marrow Aspiration

Undergo bone marrow aspiration

Bone Marrow Biopsy

Undergo bone marrow biopsy

Cytarabine

Given IV

Daunorubicin

Given IV

Echocardiography Test

Undergo ECHO

Fludarabine

Given IV

Idarubicin

Given IV

Multigated Acquisition Scan

Undergo MUGA scan

Questionnaire Administration

Ancillary studies

Venetoclax

Given PO

Primary outcome measure

  • Percentage of participants achieving measurable residual disease negative composite complete remission (CRc-MRD-) [ Time Frame: Up to 30 days post last dose of study drug ]

Central Contacts and Locations

Locations

OHSU Knight Cancer Institute

Recruiting

Portland, Oregon, United States, 97239

Contacts

Curtis A. Lachowiez

503-494-6157lachowie@ohsu.edu

Principal Investigator:

Curtis A. Lachowiez

More Information

Sponsor

OHSU Knight Cancer Institute

Last update posted

Jul 13, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by OHSU Knight Cancer Institute on 2026-07-13.