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

ConditionsAcute Myeloid LeukemiaPediatric AML
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age1-30
SponsorBaylor College of Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age Patients ≥ 1 months old to ≤ 30 years old are eligible

≥ 20% bone marrow blasts

t(8;21)(q22;q22.1) RUNX1::RUNX1T1

inv(16)(p13.1q22) or t(16;16)(p13.1;q22) CBFB::MYH11

Disqualifiers

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

Pregnancy and Breastfeeding • Female patients who are pregnant may not participate. A pregnancy test is required for female patients of childbearing potential.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Idarubicin Hydrochloride

    Drug

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

  • Fludarabine

    Drug

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

  • Cytarabine (Ara-C)

    Drug

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

  • Venetoclax

    Drug

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

  • Etoposide

    Drug

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

  • Asparaginase Erwinia Chrysanthemi (recombinant)

    Drug

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

  • Intrathecal triple

    Drug

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

  • SOC

    Other intervention

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

Treatment groups

36 Participants
are divided into 3 treatment groups
Group A: Intermediate Risk (IR) AMLExperimental treatment 7 interventions
Group B: High risk (HR) AMLExperimental treatment 5 interventions
Group C: Low risk (LR)Other 1 intervention

Trial outcomes

Primary outcomes

1

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 left ventricular systolic dysfunction or QTc prolongation, Grade 4 infection or sepsis, 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 29-36 days.

Time frame
From Day 1 of Ida-FLA through up to 50 days after completion of Ida-FLA
2

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 left ventricular systolic dysfunction or QTc prolongation, 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 29-36 days.

Time frame
From Day 1 of VIA through up to 50 days after completion of VIA
3

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 left ventricular systolic dysfunction or QTc prolongation, 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 29-36 days.

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

Secondary outcomes

1

Complete remission rate

Complete remission (CR/CRi/CRp) will be defined asbone marrow blast \<5% by morphology with regenerating normal hematopoietic cells, negative CSF cytology, and no extramedullary disease. Number of complete remission respondents.The complete remission rate will be estimated as the proportion of the Induction 2 population that is in complete remission at the end of Induction 2 for IR and HR patients A cycle of Ida-FLA(induction 2) is 29-36 days.

Time frame
at the end of Induction 2 which may occur between day 29 and day 36 of the cycle
2

MRD negative rate

The MRD assessment will be based on the subset of the Induction 2 in IR + HR population that were MRD positive at the end of Induction 1.The MRD negative rate will be estimated as the proportion of IR+HR patients who are MRD negative (\<0.05% by flow cytometry) at the end of Induction 2, out of the number of IR+HR patients who were MRD positive (\>0.05% by flow cytometry) at the end of Induction 1. A cycle of Ida-FLA(induction 2) is 29-36 days.

Time frame
at the end of Induction 2 which may occur between day 29 and day 36 of the cycle
3

3 year event-free survival

Event-free survival (EFS) is defined as the time from study enrollment until refractory disease or relapse, death due to any cause or last date of follow-up over 3 years in IR and HR, separately. The median survival time will be estimated using the Kaplan-Meier method.

Time frame
from enrollment up to 3 years
4

3 year overall survival

Overall survival (OS) is defined as time from study entry until death due to any cause or last date of follow-up over 3 years in IR and HR, separately.The median survival time will be estimated using the Kaplan-Meier method.

Time frame
From enrollment up to 3 years

Other outcomes

Sponsors and contacts

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Baylor College of Medicine

Lead sponsor

Source ClinicalTrials.gov
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