Clinical trial NCT02642965 (phase 1/phase 2, status: active, not recruiting)
Conditions: recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, therapy-related acute myeloid leukemia
ICD codes: G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2, D75.1, E26.1, N91.1, N91.4, N94.5, A51.41, A51.43, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01
Drugs: cytarabine, fludarabine phosphate, liposome-encapsulated daunorubicin-cytarabine
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, NC1=NC(F)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O, COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(C)=O)C(O)=C1C2=O
Eligibility criteria:

        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