• Pediatric, adolescent, or young adult patients who have relapse or refractory T-cell lymphoblastic leukemia (T-ALL) or T-Cell lymphoblastic lymphoma (T-LLy) according to 2017 WHO classification and NCCN v1 2021.

• Patients have adequate performance status (ECOG ≤2) for patients≥16 years old, Lansky score \>50 for patients\<16 years old.

• Patients must be 1mo to 21 years of age at time of signing/or having proxy sign the informed consent.

• Patients with asymptomatic CNS disease are eligible (see also Exclusion Criterion #2 in section 4.2.)

• The following conditions are allowed on study: conditions requiring systemic glucocorticoid use, such as autoimmune disease, acute or chronic controlled graft versus host disease (GVHD) or severe asthma. Patients are also allowed up to 5 days of glucocorticoids as cytoreduction in combination with up to 3 doses of cyclophosphamide (200 mg/m2/day) are allowed as standard pre-phase treatment up to 1 day before start of study treatment or cytarabine up to 2gm/m2. This can also be discussed with PI.

• Patients must have adequate organ function and laboratory results (obtained within 14 days of enrolment:

∙ Total serum bilirubin ≤1.5 x upper limit of normal (ULN). Patients with known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN.

‣ Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to disease.

‣ Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3 x ULN; ≤5 x ULN unless in case of suspected leukemic liver involvement

‣ Amylase, Lipase and Triglycerides must be WNL prior to administration of calaspargase pegol-mknl. If the lab values are outside the normal range, the treating physicians can discuss dosing/enrolling per PI discretion.

• Females of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (β-HCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 3 months following the last dose of study drug. Effective methods of birth control include:

∙ Birth control pills, skin patches, birth control injections, implants (placed under the skin by a health care provider)

‣ Intrauterine devices (IUDs) and intra-uterine hormone-releasing systems (IUS)

‣ Condom

‣ Abstinence

‣ Bilateral tubal occlusion/ligation or Bilateral tubal occlusion/ligation by hysteroscopy with a hysterosalpingogram to confirm the procedure's success

• Males need to inform the doctor right away if the partner becomes pregnant or suspects pregnancy. While in this study and for 90 days after the last treatment the patient should not donate sperm for the purposes of reproduction. He will need to use a condom while in this study and for 90 days after the last treatment.

• Patients must have had at least 30 days between prior hematopoietic stem cell transplant and first dose of study drug.

⁃ Patients able and willing to swallow tablets or use oral dispersible tablets. No liquid formulation is available.