NCT04326439

AflacLL1901 (CHOA-AML)

CHOA-AML: A Pilot Study for Newly Diagnosed Pediatric Patients With Acute Myeloid Leukemia (AML)

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

The investigators propose to study an Aflac-AML chemotherapy backbone prospectively to validate its use in all pediatric AML and to further evaluate the cardiotoxicity with this approach for low risk AML.

Detailed description

Advances in risk stratification and therapy, have improved the event-free survival (EFS) and overall survival (OS) for pediatric acute myeloid leukemia (AML) to approximately 50% and 65% respectively, with current treatment strategies. Patients with good response to induction and/or those who lack high-risk cytogenetic and molecular features \[classified as low-risk AML (LR-AML)\] have even better outcomes with EFS and OS approaching 70% and 85% respectively; however, treatment-related toxicities remain a major concern. Anthracycline-based therapeutic regimens expose patients to the risk of anthracycline-induced cardiotoxicity. Therefore, strategies that reduce cardiac toxicities using tailored approaches while maintaining and/or improving outcomes are needed for all patients with AML. The Children's Oncology Group (COG) regimens AAML1031 and AAML0531 utilized an anthracycline-intensive backbone for LR-AML with cumulative anthracycline doxorubicin-equivalent doses of up to 492mg/m2. However, high-risk patients treated with chemotherapy alone received an intensified induction chemotherapy (using mitoxantrone-cytarabine) but with overall reduced doses of anthracycline-equivalent (342mg/m2). The investigators piloted an institutional practice to treat all LR-AML patients with four cycle regimen (Aflac-AML) with the goal of reducing cumulative anthracycline exposure, thereby reducing the risk of cardiotoxicity, while providing three high-dose cytarabine courses. In this pilot institutional experience with this approach, they were able to maintain excellent outcomes for this low-risk group with 3-year event-free survival (EFS) and OS of 70.0% ± 0.1% and 85.5% ± 0.08% respectively, from end of course 1. Recent evolution in cytogenetic classification has further delineated risk groups in AML. Gemtuzumab ozogamicin (GO), an antibody-drug conjugate was shown to reduce relapse risk in patients with CC genotype with de-novo AML on COG study AAML0531. The investigators propose to study an Aflac-AML chemotherapy backbone prospectively to validate its use in all pediatric AML and to further evaluate the cardiotoxicity with this approach for low risk AML.

Conditions

• Acute Myeloid Leukemia
• AML, Childhood

Interventions

Type	Name	Description
DRUG	Cytarabine	100 mg/m²/dose every 12 hours IV Days 1-10
DRUG	Daunorubicin	50 mg/m²/dose IV Days 1, 3, 5
DRUG	Erwinase	25,000 International Units/m²/dose IM Days 2, 9
DRUG	Etoposide	150 mg/m²/dose IV Days 1-5
DRUG	Gemtuzumab ozogamicin	Administered as a single 3 mg/m2 dose of GO to be given between days 6-10 during Induction I for patients with CC genotype, in addition to ADE therapy.
PROCEDURE	Stem cell transplantation (SCT)	Transplantation of multipotent hematopoietic stem cells from bone marrow
DRUG	Sorafenib	200 mg/m2/dose daily, rounded to accommodate tablet size. The maximum dose will be 400 mg. Days 7 through 34.

Timeline

• Start date: 2020-01-24
• Primary completion: 2022-03-15
• Completion: 2022-03-15
• First posted: 2020-03-30
• Last updated: 2022-06-15
• Results posted: 2022-06-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study