EphB4-HSA Fusion Protein and Cytarabine /or Liposomal Vincristine in Patients With Recurrent or Refractory Acute Leukemia

Inclusion Criteria: * Confirmed diagnosis of relapsed or refractory acute leukemia (acute myeloid leukemia, acute lymphoblastic leukemia, blast crisis of chronic myeloid leukemia \[CML\], secondary AML from prior myelodysplastic syndrome \[MDS\] / myeloproliferative neoplasm \[MPN\]); minimum of 5% blasts in the bone marrow or 10% blasts in circulation * Patients with Philadelphia chromosome (Ph)+ ALL or blast crisis of CML must be refractory (not intolerant) to at least 2 second/third generation ABL kinase inhibitors (TKI) * For AML: patients must belong to one of the following ?high risk? categories: * Primary induction failure (PIF) as defined by failure to achieve at least a 50% reduction in bone marrow blasts after one cycle of high intensity, anthracycline containing induction regimen or failure to achieve complete response (CR)/complete remission with incomplete blood count recovery (CRi) after two cycles of high intensity chemotherapy * First early relapse as defined by an initial remission duration of fewer than 6 months * Second or subsequent relapse regardless of remission duration, or * Relapse after allogeneic or autologous stem cell transplantation (first relapse after stem cell transplant would be eligible, regardless of prior duration of remission) * Patients with MDS who transform to AML while on hypomethylator agents or patients with AML who progress on hypomethylator agents could be considered for arm A of this trial if * They choose not to be treated on or are ineligible for the investigator's competing trial of sEPHB4-HSA + hypomethylator (9L-16-6) * They are appropriate for high dose cytarabine treatment * For ALL: patients must belong to one of the following ?high risk? categories: * Primary refractory as defined by failure to achieve CR after induction and at least one salvage therapy * Second or subsequent relapse * Relapse after allogeneic or autologous stem cell transplantation (requirement for second relapse does not apply post-transplant) * All variants of ALL including T-ALL, B / myeloid, lymphoblastic leukemia lymphoma are eligible * Patients with myeloid diseases (AML, myeloid blast crisis of CML) will be eligible for arm A with cytarabine; patients with lymphoid diseases (ALL, lymphoid blast crisis of CML) will be eligible for arm B with liposomal vincristine; patients with leukemia of ambiguous lineage or bi-phenotypic leukemia (e.g. B/myeloid) may be treated on either arm A or B, at discretion of treating physician * Performance status Eastern Cooperative Oncology Group (ECOG) 0 to 2 * Life expectancy \> 2 months * Total bilirubin ? 3 X upper limit of normal (ULN), unless attributable to Gilbert syndrome * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) / alanine transaminase \[ALT\] (serum glutamic pyruvic transaminase \[SPGT\]) ? 5 X institutional upper limit of normal * Creatinine: glomerular filtration rate (GFR) \> 30 as calculated by modification of diet in renal disease (MDRD) equation * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) * No major surgery within 4 weeks of first dose of sEPHB4 * Peripheral blood blast count ? 30,000 at time of eligibility assessment (within 7 days of start of therapy); blast counts that increase beyond 30,000 after a patient is deemed eligible will not disqualify the patient * For subjects with prior allogeneic stem cell transplant, no evidence of active graft-versus host disease (GVHD), and must be ? 2 weeks off immunosuppressive therapy * Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: * Diagnosis of acute promyelocytic leukemia (M3 classification) * ALL patient refractory to their first induction only or their first relapse, will be excluded; they must be refractory to at least one salvage therapy, or relapse after first salvage, to be eligible * ALL patients refractory to liposomal vincristine as defined by progression while on therapy or relapse within 3 months of completion of therapy with liposomal vincristine * Prior malignancy requiring therapy within the last 12 months (excluding non-melanoma skin cancer); hormone therapy for prostate cancer or adjuvant endocrine therapy for breast cancer would not be excluded * Patient is receiving other investigational agents * Active central nervous system (CNS) disease * Definition: any patient receiving active CNS therapy (defined as more than 1 intrathecal treatment per week or current radiation therapy to brain); if patient has a history of CNS disease: must have cerebrospinal fluid (CSF) sampling within 28 days of enrollment that is negative for leukemia; intrathecal chemotherapy for patients without active CNS disease is allowed (e.g., ongoing primary or secondary prophylaxis for patients who cleared the CSF prior to study enrollment); CSF sample is not required for enrollment for patients with no history of CNS disease * Chemotherapy within 2 weeks of first dose of sEPHB4-HSA (minimum of 6 weeks for nitrosoureas and 8 weeks for bone marrow transplantation) with the following exceptions: * Hydroxyurea allowed prior to, and up to day +5 of cycle 0 of treatment (max 100 mg/kg/day) * Corticosteroids allowed until day -3 (max dexamethasone 20mg/day) * Maintenance chemotherapy for ALL allowed one week prior to start of treatment (e.g., POMP) * Grade ? 2 toxicity (other than alopecia) continuing from prior anticancer therapy, including radiation * Patients with Charcot-Marie-Tooth disease or other demyelinating diseases are excluded from the liposomal vincristine containing arm * New York Heart Association class 3 or 4 heart failure; myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis, or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEPHB4-HSA or places the patient at undue risk for treatment related complications * Uncontrolled active systemic infections * Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV); patients with HBV and/or HCV sero-positivity only will be eligible, if nucleic acid amplification testing (NAT) is negative * Warfarin (any dose) or full-dose anticoagulation with other agents (low molecular weight heparin, antithrombin agents, anti-platelet agents and full dose aspirin) within 7 days prior to first dose of study drug; patients on prophylactic doses of low-molecular weight heparin are allowed