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

NCT05955261 | Suspended Phase 2 DMC FDA Drug

• 2 other identifiers: AML23NCI-2023-04138
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 10

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

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Minimal residual disease (MRD)-negativity rate

  Will compute a binomial confidence interval for the proportion of MRD-evaluable patients who become MRD-negative (defined as MRD \< 0.1%) after induction 1.

  At day 29 after induction 1

• Incidence of death or unacceptable adverse event

  A patient is deemed to have tolerated a course of therapy if they complete that course without death or an unacceptable adverse event. Will monitor the tolerability or each course using multi-stage binomial stopping rules. Will use the method of Jung and Kim to compute 95% confidence intervals that adjust for the multi-stage monitoring.

  From initiation to completion of each course of therapy, an average of 6 weeks

Secondary Outcomes (2)

• Event-free survival

  From study enrollment to disease resistance, relapse, development of a second malignancy, or death due to any cause (up to 3 years after the last enrollment).

• Overall survival

  From protocol enrollment until death (up to 3 years after the last enrollment).

Study Arms (3)

Low Risk

EXPERIMENTAL

All eligible patients receive intervention according to the Detailed Description section with the following: Venetoclax, Cytabrine, Danunorubicin Hydrochloride, Gemtuzumab Ozogamicin, Etoposide, Mitoxantrone Hydrochloride, Gilteritinib

Drug: Venetoclax; Drug: Cytarabine; Drug: Gemtuzumab Ozogamicin; Drug: Daunorubicin Hydrochloride; Drug: Idarubicin Hydrochloride; Drug: Mitoxantrone Hydrochloride; Drug: Etoposide; Drug: Gilteritinib

Intermediate Risk

EXPERIMENTAL

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

Drug: Venetoclax; Drug: Cytarabine; Drug: Gemtuzumab Ozogamicin; Drug: Daunorubicin Hydrochloride; Drug: Fludarabine Phosphate; Drug: Idarubicin Hydrochloride; Drug: Mitoxantrone Hydrochloride; Drug: Etoposide; Drug: Gilteritinib

High Risk

EXPERIMENTAL

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

Drug: Venetoclax; Drug: Azacitidine; Drug: Cytarabine; Drug: Gemtuzumab Ozogamicin; Drug: Daunorubicin Hydrochloride; Drug: Fludarabine Phosphate; Drug: Idarubicin Hydrochloride; Drug: Etoposide; Drug: Gilteritinib

Interventions

Venetoclax 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.

Also known as: Venclextra, ABT-99

High Risk; Intermediate Risk; Low Risk

Azacitidine DRUG

Given IV over 30 minutes on days 1-5

Also known as: Mylosar, Vidaza

High Risk

Cytarabine DRUG

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

Also known as: Ara-C, Cytosar-U®

High Risk; Intermediate Risk; Low Risk

Gemtuzumab Ozogamicin DRUG

Given IV

Also known as: Mylotarg

High Risk; Intermediate Risk; Low Risk

Daunorubicin Hydrochloride DRUG

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

Also known as: FI-6339, L-lyxo-Hexopyranoside

High Risk; Intermediate Risk; Low Risk

Fludarabine Phosphate DRUG

Given IV over 30 minutes on days 1-5

Also known as: SH T 586

High Risk; Intermediate Risk

Idarubicin Hydrochloride DRUG

Given IV over 15 minutes on days 3-5

Also known as: IMI-30, Zavedos

High Risk; Intermediate Risk; Low Risk

Mitoxantrone Hydrochloride DRUG

IV over 1 hour on days 2-4

Also known as: Neotalem, Pralifan, Novantrone

Intermediate Risk; Low Risk

Etoposide DRUG

Given IV over 1 hour on days 1-5

Also known as: VP-16, Vepesid®

High Risk; Intermediate Risk; Low Risk

Gilteritinib DRUG

PO on days 8-28 (21 doses)

Also known as: Xospata

High Risk; Intermediate Risk; Low Risk

Eligibility Criteria

• Age: 29 Days - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• AbbVie: collaborator

Study Sites (10)

Valley Children's Hospital

Madera, California, 93636, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Rady Children's Hospital-San Diego

San Diego, California, 92123, United States

Location

Children's National Medical Center

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

Location

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine; Cytarabine; Gemtuzumab; Daunorubicin; methyl cis-3,4-diamino-2,3,4,6-tetradeoxy-alpha-L-lyxo-hexopyranoside Pt(II); fludarabine phosphate; Idarubicin; Mitoxantrone; Etoposide; gilteritinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Arabinonucleosides; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Anthraquinones; Anthrones; Anthracenes; Quinones; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Hiroto Inaba, MD, PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: July 21, 2023
• Study Start: July 25, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2034
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (10)