Blinatumomab for Treatment of R/R or MRD-positive CD19-Positive MPAL

Inclusion Criteria: * Subjects must have histologically or cytologically confirmed R/R CD19-positive MPAL based on the WHO criteria, OR CD19-positive MPAL in CR/CRh/CRi/CRp after at least one chemotherapy block of standard ALL or AML therapy with detectable MRD ≥ 0.1%. Primary refractory MPAL is defined by absence of CR/CRh/CRi/CRp after at least one cycle of standard AML/ALL induction therapy. A patient has relapsed MPAL if they achieved a CR/CRh/CRi/CRp after induction therapy (CR1) and has then relapsed during, or after continuation of therapy. * Age 18 years and older * Subjects who have undergone allo-HSCT are eligible if they are ≥ 4 weeks post stem cell infusion, have no evidence of GVHD \> Grade 2, and are at least ≥ 1 week off all immunosuppressive therapy * Previous cytotoxic chemotherapy (except for hydroxyurea) must have been completed at least 2 weeks prior to day 1 of treatment on the study. Subjects with hematologic malignancies are expected to have hematologic abnormalities at study entry. * ECOG performance status \< 3 * Subjects must have organ function as below: * Direct bilirubin ≤ 2.5 mg/dL * AST/ALT/Alkaline phosphatase ≤ 5 X institutional upper limit of normal * Serum creatinine ≤ 3 mg/dL * Subjects with a history of CNS leukemia must be clinically stable with a flow cytometric clear CSF in the 2 weeks prior to day 1 of blinatumomab administration. Subjects with history of CNS leukemia in Cohort A should have received one dose of intrathecal chemotherapy in the 4 weeks prior to day 1 of blinatumomab administration. Subject can receive subsequent prophylactic intrathecal chemotherapy. * Female subjects of childbearing potential must have a negative pregnancy test * Ability to understand and willingness to sign a written informed consent document * Agree to comply with the study requirements and agree to come to the clinic/hospital for required study visits Exclusion Criteria: * Subjects receiving any other investigational agents, or concurrent chemotherapy, radiation therapy, or immunotherapy not including corticosteroids or hydroxyurea * Subjects with acute leukemia with any of the following cytogenetic abnormalities: t(15;17)(q24;q21) PML/RARA, t(8;21)(q22;q22) RUNX1/RUNX1T1, inv(16)(p13q22)/t(16;16)(p13;q22) CBFB-MYH11 * A history or presence of clinically relevant CNS pathology (e.g., as epilepsy, paresis, aphasia, stroke, severe brain injuries, dementia, cerebellar disease, psychosis) * Hyperleukocytosis with \> 50,000 blasts/µL. Hydroxyurea for blast count control is permitted before starting treatment and up to maximum of 10 days after starting treatment on the study. The WBC need not reach 50,000/µL to start hydroxyurea during protocol; the decision to start hydroxyurea during this time is at the discretion of the treating physician * Active, uncontrolled infection; subjects with infection under active treatment and controlled with antimicrobials are eligible * Pregnant women * Uncontrolled undercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements