Blinatumomab and Tyrosine Kinase Inhibitor Therapy in People With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Inclusion Criteria:

* Able to give informed consent
* Age ≥ 18 years of age
* Direct bilirubin ≤2x upper limit of normal (ULN), AST and ALT ≤10x upper limit of normal (ULN). Higher bilirubin and AST/ALT levels are acceptable if thought related to Ph+ ALL.
* Histology confirmed by enrolling institution Confirmed diagnosis of acute lymphoblastic leukemia (ALL) by morphology, immunohistochemistry, and/or multiparameter flow cytometry, with confirmation of Philadelphia chromosome positivity (Ph+) by cytogenetic studies (karyotype/FISH), molecular studies (BCRABL1 fusion transcripts), or targeted RNA sequencing
* No prior therapy for ALL beyond corticosteroids, hydroxyurea, or prophylactic intrathecal/intra-Ommaya chemotherapy Acceptable end-organ function (i.e. not meeting exclusion criteria below)
* Amenable to practicing an effective method of birth control during treatment and for at least 3 months following treatment on study
* ECOG performance status 0-2

Exclusion Criteria:

* Philadelphia chromosome-negative ALL
* Mature B-cell ALL (e.g. Burkitt leukemia/lymphoma)
* Active extramedullary disease at time of study entry, including known CNS-3 disease (≥5 WBC/microliter and positive cytology or flow cytometry). Note: LP and/or CNS imaging prior to treatment initiation is not required, but if the patient is found to have active CNS-3 disease (by LP) or evidence of CNS involvement on imaging in the course of evaluation of clinical findings, enrollment is not permissible.
* Presence of known ABL kinase mutations conferring resistance to dasatinib at time of study entry, including T315I mutation. Note: ABL mutation testing prior to treatment initiation is neither recommended nor required, but if results of such mutation testing are known, enrollment of a patient with known ABL kinase mutations conferring dasatinib resistance is not permissible.
* Unable to tolerate oral medication.
* Creatinine \>1.5x upper limit of normal and estimated GFR \<30 mL/min (based on 24-hour urine collection to determine creatine clearance or CKD-EPI equation) NOTE: Meeting EITHER the blood creatinine level standard OR the estimated GFR standard (based on 24 hour urine collection OR CKD-EPI equation) is required for eligibility. Subjects are excluded only if BOTH criteria are not met.
* Heart disease meeting one or more of the following criteria:

  * New York Heart Association (NYHA) stage III or IV congestive heart failure
  * Myocardial infarction \<6 months prior to enrollment
  * History of clinically significant ventricular arrhythmia
  * History of cardiomyopathy with left ventricular ejection fraction ≤20%
  * Pre-treatment Fredericia-adjusted QTc (QTcF) of \>500 msec, unless the patient is thought to be an acceptable candidate for dasatinib after consultation with a cardiologist (including, but not limited to situations in which QTcF is thought not representative of true length of repolarization due to pre-existing bundle branch block or ventricular pacing)
* Patients with active hepatitis B infection (as manifest by either detectable hepatitis B virus DNA by PCR and/or positivity for hepatitis B surface antigen) are ineligible
* Patients with active hepatitis C infection (as manifest by detectable hepatitis C virus RNA by PCR) are ineligible. Patients with detectable antibodies to hepatitis C virus will be screened by PCR for evidence of active infection.
* Patients with HIV infection are ineligible, unless on antiretroviral therapy with undetectable HIV RNA by PCR (using an assay with sensitivity to detect levels of ≥50 copies/mL) and otherwise eligible in the determination of the investigator.
* Ongoing need for systemic T-cell suppressive therapy (e.g. corticosteroids, tacrolimus, cyclosporine for active autoimmune disease or prior solid organ transplantation)
* Concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of skin
* Uncontrolled systemic fungal, bacterial, viral or other infection
* History or presence of uncontrolled or clinically significant neurological disorders such as generalized seizure disorder or severe brain injury
* Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study.