A Study To Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations
About
A phase III randomized trial for patients with de novo AML comparing standard therapy including gemtuzumab ozogamicin GO to CPX-351 with GO, and the addition of the FLT3 inhibitor gilteritinib for patients with FLT3 mutations.
Survival in childhood Acute Myeloid Leukemia (AML) has plateaued despite maximally toxic standard therapy.
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.
Study Plan: A goal of this study is to evaluate 2 strategic objectives to improve outcomes and reduce toxicities: 1) continue to build a therapeutic backbone for all patients that improves survival through enhanced efficacy and reduced anthracycline-associated toxicities, 2) introduce target-specific therapies that improve survival without increased toxicity.
- At the time of enrollment, all patients will be randomized to receive treatment with the standard chemotherapy daunorubicin/cytarabine + GO (Arm A) or treatment with CPX-351 + GO (Arm B). During Induction 1, after results of FLT3 testing become available, those children ≥ 2 years of age with FLT3/ITD allelic ratio > 0.1 or other clinically relevant non-ITD FLT3 activating mutations will be offered participation on 2 separate arms (Arm C or Arm D) of the trial; adding gilteritinib in combination with their assigned chemotherapy backbone.
Eligibility Criteria
Inclusion Criteria
- All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment
- Age
- Patients must be less than 22 years of age at the time of study enrollment
- Diagnosis
- Patients must be newly diagnosed with de novo AML with or without extramedullary disease
- Patients and/or parents must sign a written informed consent document
Exclusion Criteria
- Patients with certain diagnoses are ineligible—please reach out to study team
- Patients must have adequate cardiac functioning
- Prior Therapy
- Patients must not have received any prior therapy besides Hydroxyurea, ATRA, Corticosteroids or Intrathecal therapy given at diagnosis
- Pregnant or lactating female patients are not allowed
Primary Investigator
Glenn Edwards, MD, is the section chief of Pediatric Hematology/Oncology, as well as the Children's Oncology Group's principal investigator for Carilion Clinic. He has over 30 years of clinical experience and is board-certified by the American Board of Pediatrics in pediatrics and pediatric hematology/oncology. He completed his fellowship at Walter Reed Army Medical Center and completed his internship and residency at Tripler Army Medical Center.
Contact Information
Wendy McCarty, CCRP
Clinical Research Coordinator
Sydnee Moses, BS
Clinical Research Coordinator
