UPDATE AML: UPdated Disease Monitoring And Treatment for Enhanced Outcomes for Pediatric AML

NCT07059975 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: H-56184 UPDATE AML
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This research study investigates the tolerability of substituting two cycles of chemotherapy into the standard pediatric acute myeloid leukemia (AML) chemotherapy treatment regimen for patients with newly diagnosed AML at intermediate-risk (IR) and high-risk (HR) of relapse. The goal is to achieve similar or better survival with chemotherapy cycles that are intensive but less likely to cause long-term complications. Patients will enroll on this trial at the end of their first induction cycle. The two cycles to be substituted are:

• "Ida-FLA" (idarubicin+fludarabine/cytarabine) as Induction 2
• "VIA" (venetoclax+idarubicin+cytarabine) as Intensification 1 of the HR treatment regimen, and Intensification 2 of the IR treatment backbone. Researchers will evaluate side effects and outcomes for up to three years after enrollment. Participants will also have the opportunity to participate in optional research studies including patient surveys and blood and bone marrow sample testing.

Conditions

Acute Myeloid Leukemia; Pediatric AML

Keywords

venetoclax; measurable residual disease (MRD); digital PCR

Outcome Measures

Primary Outcomes (3)

• Tolerability rate of Ida-FLA

  Tolerability rate is the proportion of participants in the tolerability dataset who did not experience an intolerable event during Induction 2 for IR and HR patients. Number of intolerable participants will be used. Intolerability is defined by events outlined in Section 6.6 of the protocol as follow: Non-Hematological Toxicity: Any Grade 5 toxicity, Grade 4 cardiac disorder, Grade 4 infection, or other Grade 4+ non-hematologic toxicity except: * Grade 4 nausea/vomiting (\<3 days) * Grade 4 ALT/AST/GGT elevation (returns to ≤Grade 1 before next cycle) * Grade 4 electrolyte abnormalities (corrected by supplementation) * Cycle delays \>50 days indicate intolerability. Hematologic Toxicity: Intolerability includes failure to recover ANC \>500/mL and platelets \>20,000/mL (without transfusion in past 7 days) by day 50 or cycle start delay \>50 days. A cycle of Ida-FLA is 29-56 days.

  From Day 1 of Ida-FLA through up to 50 days after completion of Ida-FLA

• Tolerability rate of VIA for IR patients

  Tolerability rate is the proportion of participants in the tolerability dataset who did not experience an intolerable event during intensification 2 for IR patients as the 4th cycle. Number of intolerable participants will be used. Intolerability is defined by events outlined in Section 6.6 of the protocol as follow: Non-Hematological Toxicity: Any Grade 5 toxicity, Grade 4 cardiac disorder, Grade 4 infection, or other Grade 4+ non-hematologic toxicity except: * Grade 4 nausea/vomiting (\<3 days) * Grade 4 ALT/AST/GGT elevation (returns to ≤Grade 1 before next cycle) * Grade 4 electrolyte abnormalities (corrected by supplementation) * Cycle delays \>50 days indicate intolerability. Hematologic Toxicity: Intolerability includes failure to recover ANC \>500/mL and platelets \>20,000/mL (without transfusion in past 7 days) by day 50 or cycle start delay \>50 days. A cycle of VIA is 29-56 days.

  From Day 1 of VIA through up to 50 days after completion of VIA

• Tolerability rate of VIA for HR patients

  Tolerability rate is the proportion of participants in the tolerability dataset who did not experience an intolerable event during intensification 2 for HR patients as the 3rd cycle. Number of intolerable participants will be used. Intolerability is defined by events outlined in Section 6.6 of the protocol as follow: Non-Hematological Toxicity: Any Grade 5 toxicity, Grade 4 cardiac disorder, Grade 4 infection, or other Grade 4+ non-hematologic toxicity except: * Grade 4 nausea/vomiting (\<3 days) * Grade 4 ALT/AST/GGT elevation (returns to ≤Grade 1 before next cycle) * Grade 4 electrolyte abnormalities (corrected by supplementation) * Cycle delays \>50 days indicate intolerability. Hematologic Toxicity: Intolerability includes failure to recover ANC \>500/mL and platelets \>20,000/mL (without transfusion in past 7 days) by day 50 or cycle start delay \>50 days. A cycle of VIA is 29-56 days.

  From Day 1 of VIA through up to 50 days after completion of VIA

Secondary Outcomes (7)

• Complete remission rate

  at the end of Induction 2 which may occur between day 29 and day 56 of the cycle

• MRD negative rate

  at the end of Induction 2 which may occur between day 29 and day 56 of the cycle

• 3 year event-free survival

  from enrollment up to 3 years

• 3 year overall survival

  From enrollment up to 3 years

• Rate of count recovery in IR Intensification 1

  at the end of Intensification 1 which may occur between day 29 and day 56 of the cycle

Study Arms (3)

Intermediate Risk (IR) AML

EXPERIMENTAL

Patients will receive Ida-FLA as Induction 2, cytarabine/etoposide ("AE") as Intensification 1, VIA as Intensification 2, and Capizzi AraC as intensification 3.

Drug: Idarubicin Hydrochloride; Drug: Fludarabine; Drug: Cytarabine (Ara-C); Drug: Venetoclax; Drug: Etoposide; Drug: Asparaginase Erwinia Chrysanthemi (recombinant); Drug: Intrathecal triple

High risk (HR) AML

EXPERIMENTAL

Patients will receive Ida-FLA as Induction 2 and VIA as Intensification 1. These patients will then proceed on to a hematopoietic stem cell transplantation if an appropriate donor is found, otherwise will receive 2 more cycles of chemotherapy following the IR regimen.

Drug: Idarubicin Hydrochloride; Drug: Fludarabine; Drug: Cytarabine (Ara-C); Drug: Venetoclax; Drug: Intrathecal triple

Low risk (LR)

OTHER

Low risk pediatric AML patients will receive standard of care chemotherapy but have the option to participate in correlative studies

Other: SOC

Interventions

Idarubicin Hydrochloride DRUG

Idarubicin is given in combination with fludarabine and cytarabine for Ida-FLA, and in combination with venetoclax and cytarabine for VIA.

High risk (HR) AML; Intermediate Risk (IR) AML

Fludarabine DRUG

Fludarabine is given in combination with idarubicin and cytarabine for Ida-FLA.

High risk (HR) AML; Intermediate Risk (IR) AML

Cytarabine (Ara-C) DRUG

Cytarabine is given in combination with other chemotherapy agents in every cycle and both arms.

High risk (HR) AML; Intermediate Risk (IR) AML

Venetoclax DRUG

Venetoclax is given in combination with idarubicin and cytarabine for VIA.

High risk (HR) AML; Intermediate Risk (IR) AML

Etoposide DRUG

Etoposide is given in combination with cytarabine for AE, as Intensification 1 for IR patients.

Intermediate Risk (IR) AML

Asparaginase Erwinia Chrysanthemi (recombinant) DRUG

Rylaze is given in combination with cytarabine for Intensification 3 for IR patients.

Intermediate Risk (IR) AML

Intrathecal triple DRUG

Methotrexate, hydrocortisone and cytarabine are combined into one preparation for intrathecal administration at multiple time points during treatment.

High risk (HR) AML; Intermediate Risk (IR) AML

SOC OTHER

Low-Risk Patients will receive Texas childern's Hospital practice standard for de novo AML.

Low risk (LR)

Eligibility Criteria

• Age: 1 Month - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \- Age Patients ≥ 1 months old to ≤ 30 years old are eligible
• Patients must be diagnosed with AML or myeloid sarcoma according to the 2022 WHO classification with or without extramedullary disease. Patients with AML must have 1 of the following at initial diagnosis:
• ≥ 20% bone marrow blasts
• In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy.
• \< 20% bone marrow blasts with one or more of the genetic abnormalities below:
• t(8;21)(q22;q22.1) RUNX1::RUNX1T1
• inv(16)(p13.1q22) or t(16;16)(p13.1;q22) CBFB::MYH11
• Translocation involving 11q23.3 KMT2A rearrangement
• t(6;9)(p23;q34.1) DEK::NUP214
• inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) MECOM rearrangement
• Megakaryoblastic with t(1;22)(p13.3;q13.3) RBM15::MRTFA
• Mutated NPM1
• t(5;11)(q35.3;p15.5) NUP98::NSD1
• inv(16)(p13.3q24.3) CBFA2T3::GLIS2
• t(11;12)(p15.5;p13.5) NUP98::KDM5A

You may not qualify if:

• \- Patients with the following constitutional conditions are not eligible:
• Fanconi anemia
• Schwachman Diamond Syndrome
• Telomere Disorders
• Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
• Germline predispositions known, or suspected by the treating physician, to increase risk of toxicity with AML therapy
• Therapy-related AML
• Patients with any of the following oncologic diagnoses are not eligible:
• Any concurrent malignancy
• Juvenile myelomonocytic leukemia
• Philadelphia chromosome positive AML
• Mixed phenotype acute leukemia
• Acute promyelocytic leukemia
• AML with FLT3 internal tandem duplication (FLT3-ITD)
• Pregnancy and Breastfeeding

Sponsors & Collaborators

• Joanna Yi: lead
• Baylor College of Medicine: collaborator

Study Sites (1)

Texas Children's Cancer and Hematology Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasm, Residual

Interventions

Idarubicin; fludarabine; Cytarabine; venetoclax; Etoposide; asparaginase erwinia chrysanthemi recombinant

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Central Study Contacts

Joanna S Yi, MD

CONTACT

832-824-6699; jsyi@texaschildrens.org

Alexandra M Stevens, MD, PhD

CONTACT

832-824-4824; amsteven@texaschildrens.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: Pilot study with assigned risk-based treatment arms, all receiving the study interventions

Study Record Dates

• First Submitted: June 18, 2025
• First Posted: July 11, 2025
• Study Start: October 22, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): August 1, 2031
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)