- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03568994
Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML) (ATACC 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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
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Baltimore, Maryland, United States, 21205
- Johns Hopkins Medicine
-
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Texas
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Houston, Texas, United States, 77030
- Baylor College of Medicine - Texas Childrens Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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,
- 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.
Exclusion Criteria:
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.
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ADE 10+3+5 plus Atovaquone (AQ)
Induction I ADE: cytarabine, daunorubicin, etoposide 10+3+5, atovaquone daily
|
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.
Other Names:
As part of routine Induction 1 chemotherapy (ADE 10+3+5)
As part of routine Induction 1 chemotherapy (ADE 10+3+5)
As part of routine Induction 1 chemotherapy (ADE 10+3+5)
|
Experimental: DA 3+10 with GO plus AQ
Induction I DA: daunorubicin, cytarabine 3+10 with GO: gemtuzumab ozogamicin, atovaquone daily
|
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.
Other Names:
As part of routine Induction 1 chemotherapy (ADE 10+3+5)
As part of routine Induction 1 chemotherapy (ADE 10+3+5)
As part of routine Induction 1 chemotherapy(DA 3+10 + GO)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma Concentrations
Time Frame: 5 weeks
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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).
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5 weeks
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Dose Omission Frequency
Time Frame: 5 weeks
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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.
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5 weeks
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Time to Achieve Steady State
Time Frame: 5 weeks
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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.
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5 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Alexandra Stevens, MD, Baylor College of Medicine - Texas Children's Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Hematologic Diseases
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Antibiotics, Antineoplastic
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Immunoconjugates
- Immunotoxins
- Etoposide
- Atovaquone
- Cytarabine
- Daunorubicin
- Gemtuzumab
Other Study ID Numbers
- H-42691
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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