26 Participants Needed

Atovaquone + Chemotherapy for Acute Myeloid Leukemia

(ATACC AML Trial)

Recruiting at 3 trial locations
Age: < 65
Sex: Any
Trial Phase: Phase < 1
Sponsor: Baylor College of Medicine
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial allows prior use of certain medications like hydroxyurea and ATRA, but they cannot be taken at the same time as the trial treatment. The protocol does not specify about other medications, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination including Atovaquone, Cytarabine, Daunorubicin, Etoposide, and Gemtuzumab Ozogamicin for treating Acute Myeloid Leukemia?

Research shows that a combination of Gemtuzumab Ozogamicin with Daunorubicin and Cytarabine has improved overall survival in patients with newly diagnosed acute myeloid leukemia compared to standard chemotherapy. Additionally, Vyxeos, a formulation of Daunorubicin and Cytarabine, demonstrated a significant survival benefit in high-risk AML patients.12345

What safety data exists for Atovaquone + Chemotherapy in treating Acute Myeloid Leukemia?

The combination of gemtuzumab ozogamicin (Mylotarg) with daunorubicin and cytarabine for acute myeloid leukemia has common side effects like bleeding and infection. Vyxeos, a combination of daunorubicin and cytarabine, shows side effects such as rash, fever, and low blood cell counts. Another combination with idarubicin, high-dose cytarabine, and etoposide was well-tolerated, with side effects like nausea and liver function changes.56789

What makes the drug Atovaquone combined with chemotherapy unique for treating acute myeloid leukemia?

This treatment is unique because it combines Atovaquone, a drug typically used for pneumonia, with standard chemotherapy to suppress energy production in leukemia cells, potentially enhancing the treatment's effectiveness. Atovaquone's ability to reduce leukemia burden by targeting oxidative phosphorylation (a process cells use to produce energy) is a novel approach in acute myeloid leukemia therapy.910111213

What is the purpose of this trial?

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.

Research Team

AS

Alexandra Stevens, MD

Principal Investigator

Baylor College of Medicine - Texas Children's Hospital

Eligibility Criteria

This trial is for children over 1 month and young adults under 21 with newly diagnosed acute myeloid leukemia (AML) that hasn't been treated before. They must have specific genetic abnormalities or a certain percentage of bone marrow blasts, among other criteria. Those who've had extensive prior anthracycline treatment, are pregnant or breastfeeding, or have certain genetic conditions like Fanconi anemia aren't eligible.

Inclusion Criteria

I have AML with more than 20% bone marrow blasts, as per WHO guidelines.
My leukemia has specific genetic features or less than 20% immature blood cells.
My myelodysplastic syndrome has progressed to acute myeloid leukemia.
See 6 more

Exclusion Criteria

I am currently pregnant.
Lactating females unless they have agreed not to breastfeed their infants
I have AML and have been treated with high doses of anthracyclines.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive induction chemotherapy with cytarabine, daunorubicin, etoposide, and atovaquone

5 weeks
Multiple visits for chemotherapy administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Atovaquone
  • Cytarabine
  • Daunorubicin
  • Etoposide
  • Gemtuzumab Ozogamicin
Trial Overview The study tests atovaquone combined with standard chemotherapy drugs (Daunorubicin, Gemtuzumab Ozogamicin, Etoposide, Cytarabine) in treating new cases of AML. It aims to see how often atovaquone doses are missed due to chemo side effects and measure the levels and timing of atovaquone in the blood during treatment.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: DA 3+10 with GO plus AQExperimental Treatment4 Interventions
Induction I DA: daunorubicin, cytarabine 3+10 with GO: gemtuzumab ozogamicin, atovaquone daily
Group II: ADE 10+3+5 plus Atovaquone (AQ)Experimental Treatment4 Interventions
Induction I ADE: cytarabine, daunorubicin, etoposide 10+3+5, atovaquone daily

Cytarabine is already approved in United States, European Union, Canada for the following indications:

🇺🇸
Approved in United States as Cytosar-U for:
  • Acute myeloid leukemia
  • Acute lymphocytic leukemia
  • Chronic myeloid leukemia
  • Meningeal leukemia
🇪🇺
Approved in European Union as Depocyt for:
  • Lymphomatous meningitis
🇨🇦
Approved in Canada as Cytosar-U for:
  • Acute myeloid leukemia
  • Acute lymphocytic leukemia
  • Chronic myeloid leukemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials
1,044
Recruited
6,031,000+

William Marsh Rice University

Collaborator

Trials
50
Recruited
28,400+

Findings from Research

In a study of 237 older patients with acute myeloid leukemia, treatment with gemtuzumab ozogamicin (GO) significantly improved overall survival (OS) compared to best supportive care, with a median OS of 4.9 months for GO versus 3.6 months for BSC.
The treatment was well-tolerated, showing similar rates of serious adverse events between the GO and BSC groups, indicating that GO can be a safe and effective first-line therapy for patients unsuitable for intensive chemotherapy.
Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial.Amadori, S., Suciu, S., Selleslag, D., et al.[2022]
In a study of 2,157 adult patients with newly diagnosed acute myeloid leukemia (AML), the overall complete remission (CR) rate was similar (69%) across three different anthracyclines: daunorubicin, idarubicin, and mitoxantrone.
However, patients treated with daunorubicin had significantly shorter disease-free survival (DFS) rates compared to those treated with idarubicin or mitoxantrone, suggesting that using either idarubicin or mitoxantrone may enhance long-term chemotherapy efficacy for AML.
Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10.Mandelli, F., Vignetti, M., Suciu, S., et al.[2022]
The combination treatment of gemtuzumab ozogamicin, intermediate-dose cytarabine, and mitoxantrone (MIDAM) resulted in a 63% overall response rate in 62 patients with refractory or relapsed CD33(+) acute myeloid leukemia, with 50% achieving complete remission.
While the MIDAM regimen showed promising efficacy, it also had safety concerns, including a 16% rate of severe hyperbilirubinemia and four early toxic deaths, highlighting the need for further randomized trials to establish its safety and effectiveness as a standard treatment.
Long-term disease-free survival after gemtuzumab, intermediate-dose cytarabine, and mitoxantrone in patients with CD33(+) primary resistant or relapsed acute myeloid leukemia.Chevallier, P., Delaunay, J., Turlure, P., et al.[2019]

References

Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial. [2022]
A comparative evaluation of gemtuzumab ozogamicin + daunorubicin-cytarabine and other treatments for newly diagnosed acute myeloid leukemia. [2019]
Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. [2022]
Long-term disease-free survival after gemtuzumab, intermediate-dose cytarabine, and mitoxantrone in patients with CD33(+) primary resistant or relapsed acute myeloid leukemia. [2019]
EMA Review of Daunorubicin and Cytarabine Encapsulated in Liposomes (Vyxeos, CPX-351) for the Treatment of Adults with Newly Diagnosed, Therapy-Related Acute Myeloid Leukemia or Acute Myeloid Leukemia with Myelodysplasia-Related Changes. [2022]
The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia. [2020]
FDA Approval Summary: (Daunorubicin and Cytarabine) Liposome for Injection for the Treatment of Adults with High-Risk Acute Myeloid Leukemia. [2020]
Idarubicin, high-dose cytarabine and etoposide for remission induction in therapy-related acute myeloid leukemia. [2019]
Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. [2022]
Repurposing Atovaquone as a Therapeutic against Acute Myeloid Leukemia (AML): Combination with Conventional Chemotherapy Is Feasible and Well Tolerated. [2023]
New chemotherapeutic agents in acute myeloid leukemia. [2013]
Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape. [2020]
13.United Statespubmed.ncbi.nlm.nih.gov
New agents for treatment of children with acute myelogenous leukemia. [2019]
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