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Acute Myeloid LeukemiaEarly Phase 1ATACC AMLNCT03568994

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

A Early Phase 1 study testing Atovaquone, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia, run by Baylor College of Medicine at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 month to 20 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Atovaquone, Cytarabine and Daunorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
2 sitesUnited States
Study dates
10 Jul 2018to 20 Sep 2025
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 month to 20 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age: Children ≥1 month and children and young adults < 21 years of age
  • Diagnosis: Patients must be newly diagnosed with acute myelogenous leukemia
  • 2.1 Patients with previously untreated primary AML who meet the customary criteria for AML with ≥ 20% bone marrow blasts as set out in the 2008 World Health Organization (WHO) Myeloid Neoplasm Classification are eligible.
  • Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive. In cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/Fluorescent in situ hybridization (FISH) testing is feasible can be substituted for the marrow exam at diagnosis
  • 2.2 Patients with < 20% bone marrow or peripheral blood blasts are eligible if they have:
  • A karyotypic abnormality characteristic of de novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities,
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  • The unequivocal presence of megakaryoblasts, or
  • Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis).
  • Pre-existing myelodysplastic syndrome:
  • Patients with a history of myelodysplastic syndrome that has progressed to AML which meets the criteria above are eligible.
  • Therapy-related or secondary AML Patients with AML which is thought to be therapy related but meet the criteria above are eligible.
  • Prior Therapy:
  • Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and IT cytarabine given at diagnosis is allowed. Hydroxyurea and ATRA cannot be given concurrently with protocol therapy. There is no specific amount of time mandated between the last dose of hydroxyurea or ATRA and the start of protocol therapy.
  • With the exception of infants who had previously received low dose cytarabine to control disease, patients who have previously received any other antileukemic therapy (i.e. chemotherapy or radiation therapy) are not eligible for this protocol.
  • Organ Function Requirement:
  • Adequate Liver Function Defined as:
  • Direct Bilirubin ≤2x upper limit of normal (ULN) for age and institution (unless related to leukemic involvement), and
  • serum glutamate-pyruvate transaminase (SGPT) (ALT) ≤2.5x ULN for age and institution (unless it is related to leukemic involvement)
  • Ability to receive enteral medication:
  • Eligible patients should have no contraindication to enteral administration of medication (e.g. oral, Nasogastric (NG), G-tube, etc) as determined by the evaluating physician.

Who cannot join

  • Excluded Constitutional Conditions
  • Patients with a history of any of the following constitutional conditions are not eligible:
  • Fanconi anemia
  • Shwachman syndrome
  • Any other known constitutional bone marrow failure syndrome
  • Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 who are eligible to receive treatment for Down Syndrome (DS) related AML Note: Enrollment and initiation of therapy may occur pending results of clinically indicated studies to exclude these conditions. If a patient is found to have any of these conditions they should be removed from the study once results are received. Patients who are removed due to ineligibility after results are received will be replaced.
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  • Other Excluded Conditions
  • Patients with any of the following oncologic diagnoses are not eligible:
  • Any concurrent malignancy
  • Juvenile myelomonocytic leukemia (JMML)
  • Philadelphia chromosome positive AML
  • Biphenotypic or bilineal acute leukemia
  • Acute promyelocytic leukemia Note: Enrollment and initiation of therapy may occur pending results of clinically indicated studies to exclude these conditions. If a patient is found to have any of these conditions they should be removed from the study once results are received. Patients who are removed due to ineligibility after results are received will be replaced.
  • Prior receipt of anthracyclines Patients with treatment-related AML who have received more than 250mg/m2 of anthracyclines (in daunorubicin equivalents) are not eligible.
  • Known Allergy or Intolerance to Atovaquone Patients with a known allergy or intolerance to atovaquone are not eligible.
  • Enrollment on another ongoing treatment study Patients who are enrolled on a treatment study are not eligible
  • Pregnancy or Breast-Feeding 6.1 Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs.
  • 6.2 Lactating females are not eligible unless they have agreed not to breastfeed their infants.
  • 6.3 Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Johns Hopkins Medicine

    Baltimore, Maryland, 21205

  • Baylor College of Medicine - Texas Childrens Hospital

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Atovaquone, Cytarabine, Daunorubicin, Etoposide, Gemtuzumab Ozogamicin
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtovaquoneDrug

    Also called Mepron

    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.

  • CytarabineDrug

    As part of routine Induction 1 chemotherapy (ADE 10+3+5)

  • DaunorubicinDrug

    As part of routine Induction 1 chemotherapy (ADE 10+3+5)

  • EtoposideDrug

    As part of routine Induction 1 chemotherapy (ADE 10+3+5)

  • Gemtuzumab OzogamicinDrug

    As part of routine Induction 1 chemotherapy(DA 3+10 + GO)

Study groups in NCT03568994
Study groupRoleWhat they receive
ADE 10+3+5 plus Atovaquone (AQ)ExperimentalInduction I ADE: cytarabine, daunorubicin, etoposide 10+3+5, atovaquone daily
DA 3+10 with GO plus AQExperimentalInduction I DA: daunorubicin, cytarabine 3+10 with GO: gemtuzumab ozogamicin, atovaquone daily
Receives: Drug: Atovaquone; Drug: Cytarabine; Drug: Daunorubicin; Drug: Gemtuzumab Ozogamicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma Concentrations

    The investigators will determine plasma levels of atovaquone at the following time points: Day 6, 11, 13, 15, 18, 20, 22, 29 and on the day of the end of induction bone marrow (BM) assessment (generally around Day 36).

    Measured: 5 weeks

  2. Dose Omission Frequency

    To quantify the frequency of atovaquone doses omitted due to standard MRC related toxicity. Administration of doses of atovaquone will be monitored while the patient is hospitalized in the electronic medical record and abstracted to case report forms. Families will also be given a diary to complete.

    Measured: 5 weeks

  3. Time to Achieve Steady State

    Time to achieving steady state concentrations of atovaquone when given in combination with standard chemotherapy in children with de novo AML will be determined using stepwise tests of linear trend.

    Measured: 5 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2018
  2. Study start10 Jul 2018
  3. Primary completion29 Sep 2020
  4. Study completion20 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Choice of Induction I regimen is at the treating physician's discretion (will be influenced based on drug availability)
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03568994
Sponsor's protocol ID
H-42691
Acronym
ATACC AML
Status last verified
Jun 2026
First submitted
31 May 2018
Last updated
23 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Conneely SE, Stevens AM. Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy. Curr Oncol Rep. 2021 Jan 13;23(2):16. doi: 10.1007/s11912-020-01009-3.

    PubMed 33439382

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Atovaquone, Cytarabine and Daunorubicin in people with Acute Myeloid Leukemia, run by Baylor College of Medicine at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma Concentrations (time frame: 5 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03568994, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.

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