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This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.
This trial tests the use of a disposable perfusion phantom (P4) to decrease errors in calculating the blood flow of a tissue with DCE-MRI. DCE-MRI is used calculate blood flow of various tissues including tumors. Blood flow often serves as a critical indicator showing a disease status. For example, a pancreatic tumor has typically low blood flow, so it can be used as an indicator to identify the presence of a pancreatic tumor. In addition, an effective therapy may result in the increase of blood flow in a pancreatic tumor during the early period of treatment. Therefore, DCE-MRI may be used to determine whether the undergoing therapy is effective or not by measuring the change of blood flow in the pancreatic tumor and may help doctors decide whether to continue the therapy or try a different one. Unfortunately, the measurement of blood flow using DCE-MRI is not accurate. The use of an artificial tissue, named "phantom" or P4, together with a patient may help to reduce errors in DCE-MRI because errors will affect the images of both the patient and the phantom. Because it is known how the blood flow of the phantom appears when no errors are present, the phantom may be used to detect what kinds of errors are present in the image, how many errors are present in the image, and how to remove errors from the image.

Wenhan Zhu, PhD

  • Assistant Professor of Pathology, Microbiology, and Immunology

Wenhan Zhu, PhD

  • Assistant Professor of Pathology, Microbiology, and Immunology

wenhan.zhu@vumc.org

Research Program

Have any questions? Contact Us 1-877-936-8422 for more information

Laura Kennedy, MD, PhD

  • Assistant Professor of Medicine (Hematology/Oncology)

Laura Kennedy, MD, PhD

  • Assistant Professor of Medicine (Hematology/Oncology)

laura.kennedy@vumc.org

Research Program

Have any questions? Contact Us 1-877-936-8422 for more information

Wei-qi Wei, MD, PhD

  • Associate Professor of Biomedical Informatics

Wei-qi Wei, MD, PhD

  • Associate Professor of Biomedical Informatics

wei-qi.wei@vumc.org

Research Program

Have any questions? Contact Us 1-877-936-8422 for more information

Elma Zaganjor, PhD

  • Assistant Professor of Molecular Physiology and Biophysics

Elma Zaganjor, PhD

  • Assistant Professor of Molecular Physiology and Biophysics

elma.zaganjor@Vanderbilt.Edu

Research Program

Have any questions? Contact Us 1-877-936-8422 for more information

Sonya Reid, MD, MPH

  • Assistant Professor of Medicine (Hematology/Oncology)
  • Assistant Director, Community Outreach and Engagement

Sonya Reid, MD, MPH

  • Assistant Professor of Medicine (Hematology/Oncology)
  • Assistant Director, Community Outreach and Engagement

sonya.reid@vumc.org

Research Program

Have any questions? Contact Us 1-877-936-8422 for more information

Maria Piazuelo, MD

  • Research Associate Professor of Medicine

Maria Piazuelo, MD

  • Research Associate Professor of Medicine

maria.b.piazuelo@vumc.org

Research Program

Have any questions? Contact Us 1-877-936-8422 for more information

Featured Speakers:

Shari Barkin, MD, MSHS

(Vanderbilt University Medical Center)

is the William K. Warren Endowed Professor in the Department of Pediatrics and the Chief of Academic General Pediatrics at the Monroe Carrell Jr. Children’s Hospital at Vanderbilt University Medical Center. She also serves as the Executive Director for the Nashville Collaborative, an academic-community partnership to develop and test two-generation obesity prevention and treatment solutions working with the Department of Parks and Recreation. Dr. Barkin’s research focus is on clinical interventions to reduce pediatric obesity during critical windows of childhood development in underserved populations.

Stephen Hursting, PhD, MPH

(UNC Lineberger Comprehensive Cancer Center)

is the AICR/WICR Distinguished Professor in the Department of Nutrition at the University of North Carolina (UNC) at Chapel Hill. He is also Professor at the UNC Nutrition Research Institute and the UNC Lineberger Comprehensive Cancer Center. Dr. Hursting’s research interests center on precision nutrition as applied to cancer prevention, particularly the molecular and metabolic mechanisms underlying obesity-cancer associations, and the interplay between obesity, metabolism, host genetics and cancer. His lab is establishing that targeting growth factor signaling pathways, inflammation-associated immunosuppression, and the gut microbiome can reverse the procancer effects of obesity.

Bette J. Caan, DrPH

(Kaiser Permanente Division of Research)

is a senior research scientist and a nutritional epidemiologist at the Kaiser Permanente Northern California Division of Research. Dr. Caan is the former Director of the Early Stage Investigator Training Program, and she directs a research program focused on body composition and energy balance risk factors. She has expertise in the assessment of diet and body composition and the conduct of dietary intervention trials, and has recently published several papers on the obesity paradox in cancer, advocating that body mass index (BMI) misclassifies patients with regard to adiposity, and is also in part responsible for the identification of the obesity paradox.

William Murphy, PhD

(UC Davis Comprehensive Cancer Center)

is a Distinguished Professor and Vice Chair of Research in the Departments of Dermatology and Internal Medicine (Division of Hematology/Oncology) at UC Davis Comprehensive Cancer Center. Dr. Murphy’s laboratory studies various aspects within cancer immunology and immunotherapy, including immune responses to pathogens. Additionally, his research also focuses on methods to make preclinical modeling more reflective of the clinical scenario by incorporating human modifying factors such as obesity, aging, and prior immune exposures. His laboratory uses multiple models (including viral) and species (ranging from mouse, feline, canine, nonhuman primate and clinical sample) to integrate/link immune signatures and responses to pathogens, immunotherapies, or immune challenges.

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