Erwinia asparaginase with chemotherapy for high‑risk adults with newly diagnosed Philadelphia‑negative acute lymphoblastic leukemia or lymphoblastic lymphoma

Inclusion Criteria:

* Documented informed consent of the participant and/or legally authorized representative
* Age between 18 and 39 with body mass index (BMI) ≥ 30 or age 40-54 years, regardless of BMI
* Eastern Cooperative Oncology Group (ECOG) ≤ 2
* Patients with newly diagnosed Philadelphia (Ph)-negative (-) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) according to World Health Organization (WHO) criteria

  * Both B- and T-cell phenotypes are allowed.
* CD20+ patients only: White blood cell count less than 25 x 10\^9/L prior to initiation of rituximab (within 14 days prior to day 1 of protocol therapy)

  * Cytoreduction with hydroxyurea or steroid or a single dose of intrathecal chemotherapy prior to treatment may be required
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 14 days prior to day 1 of protocol therapy) (unless has Gilbert's disease or related to underlying leukemia, ≤ 3 x ULN)
* Aspartate aminotransferase (AST) ≤ 3.0 x ULN (AST ≤ 5.0 x ULN if related to underlying leukemia) (within 14 days prior to day 1 of protocol therapy)

  * Note: AST ≤ 3.0 x ULN at the time of first dose of recombinant Erwinia asparaginase administration
* Alanine aminotransferase (ALT) ≤ 3.0 x ULN (ALT ≤ 5.0 x ULN if related to underlying leukemia) (within 14 days prior to day 1 of protocol therapy)

  * Note: ALT ≤ 3.0 x ULN at the time of first dose of recombinant Erwinia asparaginase administration
* Creatinine clearance of ≥ 60 mL/min per 24-hour urine test or the Cockcroft-Gault formula (within 14 days prior to day 1 of protocol therapy)
* Prothrombin (PT) ≤ 1.5 ULN (within 14 days prior to day 1 of protocol therapy)
* Activated partial thromboplastin time (aPTT) ≤ 1.5 ULN (within 14 days prior to day 1 of protocol therapy)
* Left ventricular ejection fraction (LVEF) ≥ 50%

  * Note: Echocardiogram to be performed within 42 days prior to day 1 of protocol therapy
* Seronegative for active hepatitis B virus (HBV) (surface antigen negative and anti-hepatitis B virus core antibody \[HBc\] negative) for CD20+ patients only

  * Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy)

  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential to use an effective (non-hormonal) method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy. For participants taking rituximab, effective birth control or abstinence to be used for at least 12 months after last dose

  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

Exclusion Criteria:

* Leukemia-based therapy with chemotherapy with the exception of:

  * Cytoreduction with steroid or hydroxyurea or a single dose of intrathecal chemotherapy is allowed before initiating the study
  * Prior treatment with all-trans-retinoic acid (ATRA) for suspected acute promyelocytic leukemia (APL) is allowed
* Received previous treatment with any other asparaginase formulation
* Must not have received or planning to receive live vaccine while being on study or 2 weeks before and after completion of treatment. For CD20+ patients only: Must not have received any vaccines (live or non-live) 4 weeks before rituximab
* Known presence of Philadelphia chromosome positive (Ph+; t\[9;22\])
* Class III/IV cardiovascular disability according to the New York Heart Association classification. Subjects with controlled, asymptomatic atrial fibrillation can enroll
* Parenchymal central nervous system (CNS) involvement
* Participants with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of enrollment
* History of acute cardiovascular ischemic event, i.e., myocardial infarction or unstable angina within 6 months of enrollment
* History of intracranial thrombosis or history of recurrent thrombosis or grade 3 and greater pulmonary embolism (except for catheter-related thrombosis)
* Participants with history of grade ≥ 3 pancreatitis
* History of alcohol overuse if deemed relevant in investigator opinion
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
* Uncontrolled active infection
* Clinically significant uncontrolled illness
* Other active malignancy
* Females only: Pregnant or breastfeeding
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)