Liposome-encapsulated Daunorubicin-Cytarabine, Fludarabine Phosphate, Cytarabine, and Filgrastim in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Patients must have had histologic verification of AML at original diagnosis
• Patient must have one of the following:
• Recurrent disease with >= 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease.
• Recurrent disease with an absolute blast count greater than 1,000 per microliter in the peripheral blood with or without extramedullary disease
• To be eligible for the dose-finding phase: (the dose-finding phase completed in 12/2016)
• Relapsed patients
• Patients must be in first relapse, and
• Patients must not have received prior re-induction therapy
• Refractory patients
• Patients must not have received more than one attempt at remission induction, which may consist of up to two different therapy courses; Children Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is an example
• Treatment-related AML (t-AML)
• Patients must be previously untreated for secondary AML
• To be eligible for the phase 2 efficacy phase:
• Relapse patients:
• Patients must be in first marrow relapse, and
• Patients must not have received prior re-induction therapy; donor lymphocyte infusion (DLI) is considered a re-induction attempt
• Patients must have the status of CNS1 or CNS2 only, and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy
• Patients must have a performance status corresponding to an Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients = = 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation; Note: patients must have received = = 3 months must have elapsed since transplant
• Must have received no more than 1 prior autologous or allogeneic stem cell transplant.
• Patients must be off all systemic immunosuppressive therapy for at least 2 weeks, excluding hydrocortisone for physiologic cortisol replacement
• Intrathecal cytotoxic therapy:
• No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone
• At least 14 days must have elapsed since receiving liposomal cytarabine (DepoCyte) by intrathecal injection
• Growth factors:
• Patients must not have received growth factors for 7 days prior to CPX-351
• Patients must not have received pegfilgrastim for 14 days prior to CPX-351
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age 1 to = 16 years: maximum serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL (females)
• Direct bilirubin = 27% by echocardiogram, or
• Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
• Corrected QT (using Bazett's formula [QTcB]) interval 450 mg/m^2 daunorubicin equivalents; patients who relapse after receiving AAML0531/AAML1031 therapy will be eligible for this study, provided they have not received any additional anthracyclines; NOTE: for the purposes of determining eligibility for this protocol, the following cardiotoxicity multipliers will be used to determine daunorubicin equivalents:
• Doxorubicin (doxorubicin hydrochloride): 1
• Mitoxantrone: 3
• Idarubicin: 3
• Epirubicin: 0.5
• Patients who are currently receiving another investigational drug
• Patients receiving medications for treatment of left ventricular systolic dysfunction
• Patients with any of the following diagnoses:
• Acute promyelocytic leukemia (APL)
• Down syndrome
• Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
• Wilson's disease and any other disorder of copper metabolism
• Juvenile myelomonocytic leukemia (JMML)
• Patients with documented active, uncontrolled infection at the time of study entry
• Patients with known active