Blinatumomab for Treatment of Relapsed or Refractory Mixed Phenotypic Acute Leukemia

Inclusion Criteria

• Subjects must have histologically or cytologically confirmed R/R MPAL based on World Health Organization (WHO) criteria, OR MPAL in CR/CRh/CRi/CRp after at least one chemotherapy block of standard ALL or AML treatment with MRD positivity at a level of >= 0.1% using an assay with a minimum sensitivity of 0.02%. A chemotherapy block for AML is considered one of the following, “a” or “b”: * a) an intensive induction attempt, per institution, including high-dose and/or standard-dose cytarabine +/- an anthracyclines/anthracenedione +/- an anti-metabolite, with or without growth factor or targeted therapy containing regimens. Examples include but are not limited to one cycle of high dose cytarabine (HiDAC) containing regimen, one cycle of liposomal cytarabine and daunorubicin, two cycles of standard dose cytarabine containing regimen such as 7+3 followed by 5+2. * b) for adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy: >= 2 but =< 4 cycles of Bcl-2 inhibitors in combination with azacitidine, decitabine, or low dose cytarabine, or >= 2 but =< 4 cycles of gemtuzumab ozogamicin monotherapy ** 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 graft versus host disease (GVHD) > grade 2, and are at least >= 1 week off of immunosuppressive therapy. Per Food and Drug Administration (FDA) recommendation, patients should be off of calcineurin inhibitors (CNIs) for at least 4 weeks before receiving blinatumomab
• 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. Per FDA recommendation, patients should have recovered to no more than grade 1 toxicities from prior chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status < 3
• Direct bilirubin =< 2.5 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase =< 5 X institutional upper limit of normal
• Serum creatinine =< 3 mg/dL
• Subjects with a history of central nervous system (CNS) leukemia must be clinically stable (i.e., asymptomatic with no focal neurological signs and symptoms, or signs and symptoms unchanged over 8 weeks with no > grade 2 manifestations) with a flow cytometric clear cerebrospinal fluid (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 (IT) 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/uL. Hydroxyurea for blast count control is permitted before starting treatment and up to maximum of 10 days after starting treatment on the study. The white blood count (WBC) need not reach 50,000/uL 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