Study Comparing Blinatumomab Alternating With Low-intensity Chemotherapy Versus Standard of Care Chemotherapy for Older Adults With Newly Diagnosed Philadelphia-negative B-cell Precursor Acute Lymphoblastic Leukemia

Inclusion Criteria:

• Age ≥ 55 years at the time of informed consent. OR

Age 40 to < 55 years of age if at least 1 of the following comorbidities at the time of informed consent:

• history of grades 3 and 4 pancreatitis

• diabetes mellitus with end-organ damage

• severe liver disease such as cirrhosis stage 2 with portal hypertension or historyof esophageal variceal bleeding and aspartate transaminase (AST)/alanineaminotransferase (ALT) > 10 x upper limit of normal (ULN) (liver cirrhosis must beconfirmed by biopsy)

• body mass index (BMI) ≥ 40 combined with relevant comorbidities such as metabolicsyndrome

• Any further combination of documented severe comorbidities that the investigatorjudges to be incompatible with administering an intensive pediatric based, adultadapted standard chemotherapy regimen but still compatible with the suggestedprotocol for older participants in both the experimental and the SOC arm. Theparticipant history will be reviewed by the medical monitor during screening todetermine enrollment acceptability based on a standard list with types ofcomorbidities allowed.

• Participants with newly diagnosed Philadelphia (Ph)-negative B-cell precursoracute lymphoblastic leukemia (ALL)

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, higher ECOGscore allowed if due to underlying leukemia

• All participants must have adequate organ function as defined below:

• renal: estimated glomerular filtration rate based on MDRD calculation ≥ 50mL/min/1.73 m^2

• liver function: total bilirubin ≤ 2x upper limit of normal (ULN; unless Gilbert'sDisease or if liver involvement with leukemia); exception for participants 40 to < 55 years of age if they have a comorbidity listed above: severe liver disease suchas cirrhosis stage 2 with portal hypertension or history of esophageal varicealbleeding and AST/ALT > 10 x ULN (liver cirrhosis must be confirmed by biopsy)

• cardiac: left ventricular ejection fraction (LVEF) ≥ 50% and no clinicallysignificant, uncontrolled, or active cardiovascular disease (eg, myocardialinfarction or stroke within 3 months). Consult with medical monitor as needed.

Exclusion Criteria:

• Active central nervous system (CNS) leukemia (i.e., CNS 3 leukemia, confirmed bylumbar puncture) not resolved with IT chemotherapy during screening.

• History of other malignancy within the past 3 years, with the following exceptions:

• Malignancy treated with curative intent and with no known active diseasepresent for ≥ 3 years before enrollment and felt to be at low risk forrecurrence by the treating physician Note: History of other malignancy (eg,multiple myeloma) treated with immunomodulatory drugs (eg, lenalidomide,thalidomide) in the past 3 years is an exclusion.

• Adequately treated non-melanoma skin cancer or lentigo maligna without evidenceof disease

• Adequately treated cervical carcinoma in situ without evidence of disease

• Adequately treated breast ductal carcinoma in situ without evidence of disease

• Prostatic intraepithelial neoplasia without evidence of prostate cancer

• Adequately treated urothelial papillary noninvasive carcinoma or carcinoma insitu

• Clinically relevant CNS pathology or event such as epilepsy, childhood or adultseizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson'sdisease, cerebellar disease, organic brain syndrome, or psychiatric conditions thatpreclude the use of high dose of corticosteroids

• Current autoimmune disease or history of autoimmune disease with potential CNSinvolvement

• Known infection with human immunodeficiency virus (HIV)

• Known infection with chronic or active infection with hepatitis B (eg, hepatitis bsurface [HBs] antigen reactive or quantifiable hepatitis b virus [HBV] viral load)or hepatitis C virus (HCV) (eg, HCV RNA [qualitative] is detected).

Active hepatitis B and C based on the following results:

• positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitisB or recent acute hepatitis B)

• negative HepBsAg and positive for hepatitis B core antibody: negative HBV DNA by PCRresult is necessary to enroll.

• positive Hepatitis C virus antibody (HepCAb): negative hepatitis C virus RNA by PCRresult is necessary to enroll.

• Participant with symptoms and/or clinical signs and/or radiographic and/orsonographic signs that indicate an acute or uncontrolled chronic infection.

• Cancer chemotherapy for this newly diagnosed B cell ALL before the start ofprotocol-required therapy with the exception of IT chemotherapy or optionalpre-phase (debulking) chemotherapy. Radiation to a spot lesion such as chloromaor lytic lesion of bone or vertebrae for pain or vertebral stabilization isallowed.