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 =< 16 years of age; Note: patients who are unable to walk
   because of paralysis, but who are up in a wheelchair, will be considered ambulatory
   for the purpose of assessing the performance score

   - Patients must have recovered from the acute toxic effects of all prior chemotherapy,
   immunotherapy, stem cell transplant or radiotherapy prior to entering this study; all
   prior treatment-related toxicities must have resolved to =< grade 2 prior to
   enrollment

   - Myelosuppressive chemotherapy: must not have received myelosuppressive chemotherapy
   within 3 weeks of entry onto this study (excluding hydroxyurea)

      - Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours
      prior to the start of CPX-351

   - Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with
   a biologic agent such as steroids, retinoids; Note: for agents that have known adverse
   events occurring beyond 7 days after administration (i.e. monoclonal antibodies), this
   period must be extended beyond the time during which acute adverse events are known to
   occur

   - Radiation therapy (RT): >= 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 =< than 13.6 Gray (Gy) prior radiation to the mediastinum

   - Stem cell transplant (SCT): no evidence of active graft vs. host disease for at least
   4 weeks; for allogeneic SCT patients, >= 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 < 2 years: maximum serum creatinine 0.6 mg/dL (males and females)

      - Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (males and females)

      - Age 6 to < 10 years: maximum serum creatinine 1.0 mg/dL (males and females)

      - Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (males and females)

      - Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (males) and 1.4 mg/dL
      (females)

      - Age >= 16 years: maximum serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL
      (females)

   - Direct bilirubin < 1.5 x upper limit of normal (ULN) for age and institution

   - Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x upper limit
   of normal (ULN) for age and institution (unless it is related to leukemic involvement)

   - Shortening fraction of >= 27% by echocardiogram, or

   - Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram

   - Corrected QT (using Bazett's formula [QTcB]) interval < 500 msecs

   - Patients with seizure disorder may be enrolled if on anticonvulsants and if seizures
   are well controlled

   - Central nervous system (CNS) toxicity =< grade 2

   - Patients with a known history of human immunodeficiency virus (HIV) are eligible, if
   they meet all of the following conditions:

      - No history of HIV complications with the exception of cluster of differentiation
      (CD)4 count < 200 cells/mm^3

      - No antiretroviral therapy with overlapping toxicity such as myelosuppression

      - HIV viral loads below the limit of detection

      - No history of highly active antiretroviral therapy (HAART)-resistant HIV

   - All patients and/or their parents or legal guardians must sign a written informed
   consent

   - All institutional, Food and Drug Administration (FDA), and National Cancer Institute
   (NCI) requirements for human studies must be met

Exclusion Criteria:

   - Patients who have received > 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 hepatitis B virus (HBV) and hepatitis C virus (HCV)
   infections

   - Patients with prior allergy to daunorubicin and/or cytarabine

   - Female patients who are pregnant are ineligible

   - Lactating females are not eligible

   - Female patients of childbearing potential are not eligible unless a negative pregnancy
   test result has been obtained

   - Sexually active patients of reproductive potential are not eligible unless they have
   agreed to use an effective contraceptive method for the duration of their study
   participation and for 6 months after the last dose of chemotherapy