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

NCT ID: NCT07059975

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-22
• Study Completion Date: 2031-08-31

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.

Detailed Description

UPDATE AML is a research study that investigates the tolerability of substituting two cycles of chemotherapy into the standard pediatric acute myeloid leukemia (AML) chemotherapy treatment regimen for patients at intermediate-risk (IR) and high-risk (HR) of the leukemia coming back ("relapse"). Newly diagnosed patients will receive standard Induction 1 treatment off study. If they do not have a FLT3-ITD mutation, they will be eligible to complete treatment on the UPDATE AML study. Patients considered Low Risk will receive the standard treatments outside of the UPDATE AML trial but will be eligible for the non-treatment parts of the trial. IR and HR patients will receive a combination of idarubicin, fludarabine, cytarabine (Ida-FLA) as their 2nd cycle of chemotherapy ("Induction 2"). This combination has shown desirable anti-leukemic activity in children whose leukemia has relapsed but has not yet been studied extensively in children newly diagnosed with AML. Secondly the trial will administer the new drug venetoclax (FDA approved for adults with AML but not for pediatric patients) combined with idarubicin and cytarabine as the 3rd or 4th cycle (of the HR or IR regimens respectively). Texas Children's Hospital will be providing the venetoclax.

The other major goal of UPDATE AML is to improve to detection of residual leukemia. Currently, the intensity of treatment for pediatric patients with AML depends on the genetic changes in the leukemia cells and their response to the first month of therapy. Of patients who have no detectable residual disease at the end of the first month, 30% of them will still relapse, indicating residual leukemia was still present, just not detected. Our study will develop individualized tests for each patient's genetic change which should increase detection of tiny amounts of residual leukemia. If our trial can successfully develop these individualized tests, future pediatric AML trials will incorporate these tests into use for all patients.

The research study procedures include screening for eligibility study treatment, evaluation, administration of the substituted chemotherapy cycles, and follow-up visits. Participants will be offered the possibility to provide additional blood and bone marrow samples (to be collected only at times of regular medical examination). There are additional surveys patients and parents can participate in, to understand the challenges facing families undergoing pediatric AML treatment.

Besides the 2 substituted chemotherapy cycles, patients will otherwise receive standard chemotherapy as their relapse risk indicates. Patients will be followed for approximately 3 years from enrollment.

It is expected that about 36 people will take part in this research study.

Conditions

Acute Myeloid Leukemia; Pediatric AML

Study Design

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

Study Groups

Intermediate Risk (IR) AML

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

Group Type: EXPERIMENTAL

Idarubicin Hydrochloride

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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

Cytarabine (Ara-C)

Intervention Type: DRUG

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

Venetoclax

Intervention Type: DRUG

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

Etoposide

Intervention Type: DRUG

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

Asparaginase Erwinia Chrysanthemi (recombinant)

Intervention Type: DRUG

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

Intrathecal triple

Intervention Type: DRUG

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

High risk (HR) AML

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.

Group Type: EXPERIMENTAL

Idarubicin Hydrochloride

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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

Cytarabine (Ara-C)

Intervention Type: DRUG

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

Venetoclax

Intervention Type: DRUG

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

Intrathecal triple

Intervention Type: DRUG

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

Low risk (LR)

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

Group Type: OTHER

SOC

Intervention Type: OTHER

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

Interventions

Idarubicin Hydrochloride

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

Intervention Type: DRUG

Fludarabine

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

Intervention Type: DRUG

Cytarabine (Ara-C)

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

Intervention Type: DRUG

Venetoclax

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

Intervention Type: DRUG

Etoposide

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

Intervention Type: DRUG

Asparaginase Erwinia Chrysanthemi (recombinant)

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

Intervention Type: DRUG

Intrathecal triple

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

Intervention Type: DRUG

SOC

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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:

1. ≥ 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.

2. < 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

3. A complete blood count (CBC) documenting the presence of at least 1,000/µL circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (i.e., a WBC count ≥ 10,000/μL with ≥ 10% blasts or a WBC count of ≥ 5,000/μL with ≥ 20% blasts).

4. Biopsy-proven myeloid sarcoma with or without bone marrow involvement.

Note: patients with newly diagnosed AML, myelodysplasia-related (that are not from conditions listed in protocol section 4.2.1) ARE eligible while patients with therapy-related AML are excluded.

Prior Therapy Patients must receive DA10+GO (Cytarabine days 1-10 + Daunorubicin days 1,3,5 [DA10] + Gemtuzumab ozogamcin [GO]) as prescribed in AAML1831 or the TXCH practice standard for Induction 1. Patients may have received any number of intrathecal treatments and have any CNS status at the time of enrollment.

Performance Status Patients must have a performance status corresponding to Karnofsky/Lansky score >40. (Use Karnofsky for patients ≥16 years of age and Lanksy for patients <16 years of age.)

Organ Function Requirements All laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated. Laboratory values used to assess eligibility must be no older than seven (7) days at the start of therapy. Laboratory tests need not be repeated if therapy starts within seven (7) days of obtaining labs to assess eligibility. If a post-enrollment lab value is outside the limits of eligibility, or laboratory values are > seven (7) days old, then the following laboratory evaluations must be re-checked within 48 hours prior to initiating therapy: CBC with differential, bilirubin, ALT (SGPT) and serum creatinine. If the recheck is outside the limits of eligibility, the patient may not receive protocol therapy and will be considered off protocol therapy.

Adequate renal function defined as:

• A creatinine clearance or GFR ≥ 60 ml/min/1.73m2

Adequate liver function defined as:

• A direct bilirubin < 2 mg/dL

• ALT <5x ULN or 225 U/L, with the ULN being 45 U/L for the purpose of this study.

Adequate coagulation defined as:

• INR ≤ 1.5

Adequate cardiac function defined as:

• Ejection fraction (EF) ≥ 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) ≥ 24%, within 14 days prior to planned start of Induction 2 therapy.
• For patients with cardiac dysfunction (EF < 50% or SF <24% if EF is unavailable) prior to enrollment, if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF ≥ 50%, the patient is eligible to enroll.

Informed Consent All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

Exclusion Criteria

• 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

• Female patients who are pregnant may not participate. A pregnancy test is required for female patients of childbearing potential.
• Lactating females who plan to breastfeed their infants are not eligible.
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation are not eligible.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

Joanna Yi

OTHER

Sponsor Role: lead

Responsible Party

Joanna Yi

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Texas Children's Cancer and Hematology Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Joanna S Yi, MD

Role: CONTACT

jsyi@texaschildrens.org

832-824-6699

Alexandra M Stevens, MD, PhD

Role: CONTACT

amsteven@texaschildrens.org

832-824-4824

Facility Contacts

Joanna S Yi, MD

Role: primary

jsyi@texaschildrens.org

832-824-6699

Alexandra M Stevens, MD, PhD

Role: backup

amsteven@texaschildrens.org

832-824-4824

Other Identifiers

H-56184 UPDATE AML

Identifier Type: -

Identifier Source: org_study_id