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

NCT ID: NCT05955261

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-25
• Study Completion Date: 2034-03-31

Brief 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

Detailed 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.

Conditions

Acute Myeloid Leukemia

Study Design

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

Study Groups

Low Risk

All eligible patients receive intervention according to the Detailed Description section with the following:

Venetoclax, Cytabrine, Danunorubicin Hydrochloride, Gemtuzumab Ozogamicin, Etoposide, Mitoxantrone Hydrochloride, Gilteritinib

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax will be given with each course of therapy. Patients with low-risk AML will receive four courses of therapy, intermediate-risk patients will receive five courses of therapy, and high-risk patients will receive two or three courses of therapy followed by hematopoietic stem cell transplantation.

Cytarabine

Intervention Type: DRUG

Given IV over 30 minutes q12 hours on days 1-8 (16 doses)

Gemtuzumab Ozogamicin

Intervention Type: DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type: DRUG

IV over 1 hour on days 1, 3, and 5

Idarubicin Hydrochloride

Intervention Type: DRUG

Given IV over 15 minutes on days 3-5

Mitoxantrone Hydrochloride

Intervention Type: DRUG

IV over 1 hour on days 2-4

Etoposide

Intervention Type: DRUG

Given IV over 1 hour on days 1-5

Gilteritinib

Intervention Type: DRUG

PO on days 8-28 (21 doses)

Intermediate Risk

All eligible patients receive intervention according to the Detailed Description section with the following:

Venetoclax, Cytabrine, Danunorubicin Hydrochloride, Fludarabine Phosphate, Gemtuzumab Ozogamicin, Etoposide, Idarubin Hydrochloride, Mitoxantrone Hydrochloride, Gilteritinib

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax will be given with each course of therapy. Patients with low-risk AML will receive four courses of therapy, intermediate-risk patients will receive five courses of therapy, and high-risk patients will receive two or three courses of therapy followed by hematopoietic stem cell transplantation.

Cytarabine

Intervention Type: DRUG

Given IV over 30 minutes q12 hours on days 1-8 (16 doses)

Gemtuzumab Ozogamicin

Intervention Type: DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type: DRUG

IV over 1 hour on days 1, 3, and 5

Fludarabine Phosphate

Intervention Type: DRUG

Given IV over 30 minutes on days 1-5

Idarubicin Hydrochloride

Intervention Type: DRUG

Given IV over 15 minutes on days 3-5

Mitoxantrone Hydrochloride

Intervention Type: DRUG

IV over 1 hour on days 2-4

Etoposide

Intervention Type: DRUG

Given IV over 1 hour on days 1-5

Gilteritinib

Intervention Type: DRUG

PO on days 8-28 (21 doses)

High Risk

All eligible patients receive intervention according to the Detailed Description section with the following:

Venetoclax, Azacitidine, Cytabrine, Danunorubicin Hydrochloride, Fludarabine Phosphate, Gemtuzumab Ozogamicin, Etoposide, Idarubin Hydrochloride, Gilteritinib

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax will be given with each course of therapy. Patients with low-risk AML will receive four courses of therapy, intermediate-risk patients will receive five courses of therapy, and high-risk patients will receive two or three courses of therapy followed by hematopoietic stem cell transplantation.

Azacitidine

Intervention Type: DRUG

Given IV over 30 minutes on days 1-5

Cytarabine

Intervention Type: DRUG

Given IV over 30 minutes q12 hours on days 1-8 (16 doses)

Gemtuzumab Ozogamicin

Intervention Type: DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type: DRUG

IV over 1 hour on days 1, 3, and 5

Fludarabine Phosphate

Intervention Type: DRUG

Given IV over 30 minutes on days 1-5

Idarubicin Hydrochloride

Intervention Type: DRUG

Given IV over 15 minutes on days 3-5

Etoposide

Intervention Type: DRUG

Given IV over 1 hour on days 1-5

Gilteritinib

Intervention Type: DRUG

PO on days 8-28 (21 doses)

Interventions

Venetoclax

Venetoclax will be given with each course of therapy. Patients with low-risk AML will receive four courses of therapy, intermediate-risk patients will receive five courses of therapy, and high-risk patients will receive two or three courses of therapy followed by hematopoietic stem cell transplantation.

Intervention Type: DRUG

Azacitidine

Given IV over 30 minutes on days 1-5

Intervention Type: DRUG

Cytarabine

Given IV over 30 minutes q12 hours on days 1-8 (16 doses)

Intervention Type: DRUG

Gemtuzumab Ozogamicin

Given IV

Intervention Type: DRUG

Daunorubicin Hydrochloride

IV over 1 hour on days 1, 3, and 5

Intervention Type: DRUG

Fludarabine Phosphate

Given IV over 30 minutes on days 1-5

Intervention Type: DRUG

Idarubicin Hydrochloride

Given IV over 15 minutes on days 3-5

Intervention Type: DRUG

Mitoxantrone Hydrochloride

IV over 1 hour on days 2-4

Intervention Type: DRUG

Etoposide

Given IV over 1 hour on days 1-5

Intervention Type: DRUG

Gilteritinib

PO on days 8-28 (21 doses)

Intervention Type: DRUG

Other Intervention Names

Venclextra; ABT-99; Mylosar; Vidaza; Ara-C; Cytosar-U®; Mylotarg; FI-6339; L-lyxo-Hexopyranoside; SH T 586; IMI-30; Zavedos; Neotalem; Pralifan; Novantrone; VP-16; Vepesid®; Xospata

Eligibility Criteria

Inclusion Criteria

• Diagnosis of AML fulfilling the criteria of the WHO classification of myeloid neoplasms or < 20% marrow myeloblasts and evidence of a clonal de novo AML genetic abnormality 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 and hydroxyurea 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 an effective contraceptive method during the study and for 6 months after study treatment
• Written informed consent from the patient and/or parent/legal guardian
• Direct bilirubin ≤ 1.5 x institutional upper limit of normal

Exclusion Criteria

• Patients with treatment-related AML, Down syndrome, acute promyelocytic leukemia, chronic myeloid leukemia in blast crisis, juvenile myelomonocytic leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failure syndromes are not eligible
• Uncontrolled systemic fungal, bacterial, or viral infection or significant concurrent disease that would compromise patient safety or compliance, study participation, 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.

• Minimum Eligible Age: 29 Days
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hiroto Inaba, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

Valley Children's Hospital

Madera, California, United States

Children's Hospital of Orange County

Orange, California, United States

Rady Children's Hospital-San Diego

San Diego, California, United States

Children's National Medical Center

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

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Countries

United States

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NCI-2023-04138

Identifier Type: REGISTRY

Identifier Source: secondary_id

AML23

Identifier Type: -

Identifier Source: org_study_id