liposomal cytarabine-daunorubicin cpx-351 in treating patients with untreated myelodysplastic syndrome or acute myeloid leukemia

Conditions: Acute Biphenotypic Leukemia; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

Summary: this randomized clinical trial studies liposomal cytarabine-daunorubicin cpx-351 in treating patients with untreated myelodysplastic syndrome or acute myeloid leukemia. drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin cpx-351, 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.

primary objectives: i. estimate whether the 32 units/m\^2 or the 64 units/m\^2 or both dose levels of cpx-351 (liposomal cytarabine-daunorubicin cpx-351) are likely to improve treatment-related mortality (trm) rate while keeping the complete remission (cr) rate constant in patients with untreated high-risk myelodysplastic syndrome (mds) or non-acute promyelocytic leukemia (apl) acute myeloid leukemia (aml) at high risk of trm. secondary objectives: i. describe the cr/cr with incomplete platelet count recovery (crp) rate after up to 4 cycles of induction/re-induction therapy. ii. describe the event-free survival, disease-free survival, and overall survival of patients who achieve cr/crp. iii. estimate the frequency and severity of regimen-associated toxicities. outline: patients are randomized to 1 of 2 treatment arms. arm i: induction/re-induction: patients receive lower-dose liposomal cytarabine-daunorubicin cpx-351 intravenously (iv) over 90 minutes on days 1, 3, and 5. treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. patients achieving cr or crp continue on to consolidation. consolidation: patients receive lower-dose liposomal cytarabine-daunorubicin cpx-351 iv over 90 minutes on days 1 and 3. treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. arm ii: (closed to accrual effective 4/21/14) induction/re-induction: patients receive higher-dose liposomal cytarabine-daunorubicin cpx-351 iv over 90 minutes on days 1, 3, and 5. treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. patients achieving cr or crp continue on to consolidation. consolidation: patients receive higher-dose liposomal cytarabine-daunorubicin cpx-351 iv over 90 minutes on days 1 and 3. treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed up for 1 month.

Eligibility criteria:
inclusion criteria: * diagnosis of untreated "high-risk" mds (\>= 10% blasts) or aml other than acute promyelocytic leukemia (apl) with t(15;17)(q22;q12) or variants according to the 2008 world health organization (who) classification; patients with biphenotypic aml are eligible; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution and cytogenetic/molecular information is available * prior hydroxyurea for aml is permitted but should be discontinued prior to start of cpx-351 treatment * azacitidine, decitabine, lenalidomide, and growth factors are permitted for low-risk mds (\< 10% blasts); all treatments for mds should be discontinued prior to start of cpx-351 treatment * treatment-related mortality (trm) score \>= 13.1 as calculated with simplified model * bilirubin \< 2.0 mg/ml x upper limit of normal; this requirement reflects the excretion of cpx-351 by the liver * aspartate aminotransferase (ast)/alanine aminotransferase (alt) \< 4.0 x upper limit of normal; this requirement reflects the excretion of cpx-351 by the liver * left ventricular ejection fraction (lvef) \>= 40%, assessed within 28 days prior to registration, e.g. by multi gated acquisition (muga) scan or echocardiography, or other appropriate diagnostic modality * patients with symptoms/signs of hyperleukocytosis or white blood cell (wbc) \> 100,000/ul can be treated with leukapheresis prior to enrollment * provide signed written informed consent exclusion criteria: * refractory/relapsing blast crisis of chronic myelogenous leukemia (cml) * concomitant illness associated with a likely survival of \< 1 year * active systemic fungal, bacterial, viral, or other infection, unless under treatment with anti-microbials and controlled/stable, as defined as being afebrile and hemodynamically stable for 24-48 hours