Acute Lymphoblastic Leukemia (ALL) Clinical Trials

∙ \- 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 history of esophageal variceal bleeding and aspartate transaminase (AST)/alanine aminotransferase (ALT) \> 10 x upper limit of normal (ULN) (liver cirrhosis must be confirmed by biopsy)

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

• Any further combination of documented severe comorbidities that the investigator judges to be incompatible with administering an intensive pediatric based, adult adapted standard chemotherapy regimen but still compatible with the suggested protocol for older participants in both the experimental and the SOC arm. The participant history will be reviewed by the medical monitor during screening to determine enrollment acceptability based on a standard list with types of comorbidities allowed.

‣ Participants with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL)

⁃ Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, higher ECOG score 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 ≥ 50 mL/min/1.73 m\^2

• liver function: total bilirubin ≤ 2x upper limit of normal (ULN; unless Gilbert's Disease 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 such as cirrhosis stage 2 with portal hypertension or history of esophageal variceal bleeding and AST/ALT \> 10 x ULN (liver cirrhosis must be confirmed by biopsy)

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