NCT03568994

Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML)

A Trial of Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML) in Children, Adolescents, and Young Adults (ATACC AML)

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 1 Month – 20 Years
• Healthy volunteers: Not accepted

Summary

This study will test daily dosing of atovaquone at established pneumocystis jiroveci pneumonia (PJP) prophylaxis dosing in combination with standard induction chemotherapy for de novo AML. The primary objectives are to determine the frequency of omission of atovaquone doses due to standard induction chemotherapy toxicity, to quantify the steady-state plasma levels of atovaquone, and to determine the time to achievement of steady state atovaquone levels in this population.

Detailed description

Standard cytotoxic chemotherapy is based on the Medical Research Council (MRC) backbone of cytarabine, and daunorubicin. This combination of chemotherapy is highly myelosuppressive and can lead to oral aversions, dietary intolerance, and gastrointestinal infections necessitating holding of oral drugs. Because of the toxicity of the best currently available therapy, new drugs that are considered for incorporation into existing treatment regimens will ideally have a tolerable side effect profile. This study will evaluate the tolerability of incorporating the orally bioavailable drug atovaquone in combination with standard cytotoxic induction chemotherapy for newly diagnosed pediatric AML patients. Therefore, quantifying the frequency with which atovaquone is held due to a side effect of therapy is crucial information to gather in this population.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Atovaquone	Patients will receive standard of care MRC based Induction chemotherapy (such as ADE 10+3+5 with daily atovaquone dosing starting on day 6. In order to accommodate potential drug shortages modifications to ADE 10+3+5 that retain the MRC based induction backbone regimen of DA are allowed (see second Arm). These include but are not limited to substitution of etopophos for etoposide, exclusion of etoposide, use of CPX-351 (VYXEOS (daunorubicin and cytarabine) liposome) only, and daunorubicin and cytarabine (DA) + gemtuzumab ozogamicin (GO). Patients will be monitored for adherence to and tolerance of daily dosing of atovaquone. Peripheral blood (PB) and bone marrow plasma samples will be obtained to measure atovaquone concentrations.
DRUG	Cytarabine	As part of routine Induction 1 chemotherapy (ADE 10+3+5)
DRUG	Daunorubicin	As part of routine Induction 1 chemotherapy (ADE 10+3+5)
DRUG	Etoposide	As part of routine Induction 1 chemotherapy (ADE 10+3+5)
DRUG	Gemtuzumab Ozogamicin	As part of routine Induction 1 chemotherapy(DA 3+10 + GO)

Timeline

• Start date: 2018-07-10
• Primary completion: 2020-09-29
• Completion: 2025-09-20
• First posted: 2018-06-26
• Last updated: 2026-01-27

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study