A Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia

Last updated: July 24, 2026
Sponsor: St. Jude Children's Research Hospital
Overall Status: Suspended

Phase

2

Condition

Acute Myeloid Leukemia

Platelet Disorders

Leukemia

Treatment

Daunorubicin Hydrochloride

Cytarabine

Gemtuzumab Ozogamicin

Clinical Study ID

NCT05955261
AML23
NCI-2023-04138
  • Ages 29-21
  • All Genders

Study Summary

This is a phase 2 study to test the hypothesis that venetoclax in combination with standard chemotherapy will be tolerable and active in pediatric patients with newly diagnosed acute myeloid leukemia (AML).

Primary Objectives:

  • Establish the tolerability adding venetoclax to standard chemotherapy in pediatric patients with AML

  • Estimate the proportion of patients who become minimal residual disease (MRD) negative by flow cytometry after one course of venetoclax-based induction therapy

Secondary Objectives:

  • Estimate the rates of complete remission (CR), event-free survival (EFS), and overall survival (OS) in pediatric patients who receive venetoclax-based chemotherapy

Eligibility Criteria

Inclusion

Patients with preexisting conditions that may affect chemotherapy tolerance (e.g., bone marrow failure syndrome, cardiac disease, pulmonary disease, and history of significant hepatic impairment) should be discussed with study PI in detail to enable review of the medical history prior to enrollment onto AML23 study.

Inclusion Criteria:

  • Diagnosis of AML fulfilling the criteria of the WHO classification of myeloidneoplasms or < 20% marrow myeloblasts and evidence of a clonal de novo AML geneticabnormality or myeloid sarcoma or primary myelodysplastic syndrome (MDS) with ≥ 10%blasts or a complete blood count with the presence of at least 1,000 blasts/μL (e.g., a WBC count ≥ 10,000/μL with ≥ 10% blasts or a WBC count ≥ 5,000/μL with ≥ 20% blasts

  • Age > 28 days and < 22 years

  • No prior therapy for this malignancy except for one dose of intrathecal therapy andhydroxyurea or low-dose cytarabine (≤ 200 mg/m^2 per day for ≤ 7 days)

  • Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment

  • Male and female participants of reproductive potential must agree to use aneffective contraceptive method during the study and for 6 months after studytreatment

  • Written informed consent from the patient and/or parent/legal guardian

  • Direct bilirubin ≤ 1.5 x institutional upper limit of normal

Exclusion

Exclusion Criteria:

  • Patients with treatment-related AML, Down syndrome, acute promyelocytic leukemia,chronic myeloid leukemia in blast crisis, juvenile myelomonocytic leukemia, Fanconianemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failuresyndromes are not eligible

  • Uncontrolled systemic fungal, bacterial, or viral infection or significantconcurrent disease that would compromise patient safety or compliance, studyparticipation, follow up, or interpretation of study results

  • Prior exposure to any dose of anthracycline or anthracenedione

  • Patients may not receive strong or moderate CYP3A inducers, such as rifampin, within 3 days of enrollment

  • Patients may not receive moderate or strong CYP3A inhibitors (e.g., ketoconazole,itraconazole, voriconazole, posaconazole) within 3 days of enrollment.

Study Design

Total Participants: 70
Treatment Group(s): 10
Primary Treatment: Daunorubicin Hydrochloride
Phase: 2
Study Start date:
July 25, 2023
Estimated Completion Date:
March 31, 2034

Study Description

Treatment will be based on genetic characteristics and response to therapy. Venetoclax will be given with each course of therapy. Low-risk patients will receive four courses of chemotherapy and intermediate-risk patients will receive five courses. High-risk patients who do not have a suitable stem cell donor or who decline HCT will receive five courses of chemotherapy. The definition of suitable stem cell donor and the conditioning regimens used for HCT will be determined by local institutional protocols or guidelines.

Intervention:

Low Risk

Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.

Induction 2: Venetoclax PO QD on days 1-14, cytarabine IV over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, and etoposide IV over 1 hour QD on days 1-5.

Intensification: Venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-4, and mitoxantrone hydrochloride IV over 1 hour QD on days 2-4 during intensification 1 and then venetoclax PO QD on days 1-7 and high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 during intensification 2. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28 during intensification 1 and 2.

Intermediate Risk

Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.

Induction 2: Venetoclax PO QD on days 1-14, fludarabine phosphate IV over 30 minutes QD on days 1-5, cytarabine IV over 3 hours QD starting 4 hours after each dose of fludarabine on days 1-5, idarubicin hydrochloride IV over 15 minutes QD on days 3-5. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28.

Intensification: Venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-4, and mitoxantrone hydrochloride IV over 1 hour QD on days 2-4 during intensification 1, venetoclax PO QD on days 1-7 and high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 during intensification 2, and then venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-5, and etoposide IV over 1 hour QD on days 1-5 during intensification 3. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28 during intensification 1-3.

High Risk

Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.

Induction 2: Venetoclax PO QD on days 1-14, fludarabine phosphate IV over 30 minutes QD on days 1-5, cytarabine IV over 3 hours QD starting 4 hours after each dose of fludarabine on days 1-5, idarubicin hydrochloride IV over 15 minutes QD on days 3-5. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28.

Intensification: Patients with MRD < 0.1% proceed directly to HCT if donor is available. If a donor is not yet available, patients with MRD < 0.1% may receive ventoclax PO QD on days 1-21 and azacitidine IV over 30 minutes QD on days 1-5 or venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-5, and etoposide IV over 1 hour QD on days 1-5. Patients with MRD 0.1% to < 1% may receive ventoclax PO QD on days 1-21 and azacitidine IV over 30 minutes QD on days 1-5 or venetoclax PO QD on days 1-7, cytarabine IV over 1-2 hours every 12 hours on days 1-5, and etoposide IV over 1 hour QD on days 1-5. Patients with MRD >= 1% may receive venetoclax PO QD on days 1-10, azacitidine IV over 30 minutes QD on days 1-5, and high-dose cytarabine IV over 3 hours every 12 hours on days 6, 8, and 10. Patients with FLT3 activation receive gilteritinib PO QD on days 8-28.

Connect with a study center

  • Valley Children's Hospital

    Madera, California 93636
    United States

    Site Not Available

  • Children's Hospital of Orange County

    Orange, California 92868
    United States

    Site Not Available

  • Rady Children's Hospital-San Diego

    San Diego, California 92123
    United States

    Site Not Available

  • Children's National Medical Center

    Washington D.C., District of Columbia 20020
    United States

    Site Not Available

  • Ann & Robert H. Lurie Children's Hospital

    Chicago, Illinois 60611
    United States

    Site Not Available

  • Dana-Farber Cancer Institute

    Boston, Massachusetts 02115
    United States

    Site Not Available

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina 28204
    United States

    Site Not Available

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio 45229
    United States

    Site Not Available

  • St. Jude Children's Research Hospital

    Memphis, Tennessee 38105
    United States

    Site Not Available

  • Cook Children's Medical Center

    Fort Worth, Texas 76104
    United States

    Site Not Available

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