The purpose of this study is to learn more about LP-118 (an experimental drug) and its side effects and decide on acceptable doses. The purpose of this study is to determine if LP-118 can be given safely with another medicine called ponatinib, that is FDA-approved for the treatment of acute lymphoblastic leukemia.

The purpose of this study is to learn more about LP-118 (an experimental drug) and its side effects and decide on acceptable doses. The purpose of this study is to determine if LP-118 can be given safely with another medicine called ponatinib, that is FDA-approved for the treatment of acute lymphoblastic leukemia.

This study will investigate the combination of LP-118 and ponatinib at different dose levels to find the best doses that can be safely given to patients. This means that enrolled subjects will receive progressive increasing or decreasing doses of these drugs until the maximally tolerated dose is determined. All participants will also receive a standard of care chemotherapy combination consisting of the FDA approved drugs vincristine, dexamethasone and intrathecal (injection into the spinal canal, also called "spinal tap") methotrexate. This combination is standard of care for relapsed T-ALL/LBL.

Inclusion Criteria:

1. Relapsed or refractory patients with T-lineage acute lymphoblastic leukemia or T-lymphoblastic lymphoma

2. 18 years old or older

3. Bone marrow or peripheral blood involvement with ≥5% lymphoblasts or measurable residual disease with >10-4 level detected by multiparameter flow cytometry or next-generation sequencing (NGS)-based measurable residual disease (ClonoSEQ, Adaptive Technologies). Patients with isolated extramedullary disease that is measurable by computed tomography (CT) scan are also eligible.

4. Eastern Cooperative Oncology Group performance status 0-2.

5. Adequate organ function as defined by all of the following:

   1. Creatinine clearance ≥50 mL/min, determined by the Cockroft-Gault formula, or measured by a 24-hour urine collection.
   2. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN) and bilirubin ≤1.5 x ULN (unless considered due to Gilbert's syndrome or of non-hepatic origin i.e,, leukemic involvement). For patients with Gilbert's syndrome, bilirubin ≤1.5 x of their baseline bilirubin level will be required.

6. Participants must be at least 2 weeks from major surgery or radiation therapy. A wash-out period of 4 half-lives is required for patients who participated in other investigational trials. These patients must have recovered from clinically significant toxicities related to these prior treatments.

7. Participants must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

8. Females of childbearing potential will use effective contraception during protocol treatment and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during protocol treatment and for at least 5 months after the last dose. A patient is of childbearing potential if, in the opinion of the treating investigator, he/she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential (ie, meet at least one of the following criteria):

   a. Have undergone hysterectomy or bilateral oophorectomy; or have medically confirmed ovarian failure; or are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause).

9. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Active central nervous system (CNS) leukemia
2. Active or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV). Patients with HIV but an undetectable viral load are eligible for enrollment.
3. Major surgery within <2 weeks before randomization.
4. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition.
5. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for ≥2 years or are not currently requiring treatment.
6. Uncontrolled cardiac disease.
7. Pregnant females; breastfeeding females; males with female partners of reproductive potential and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for a minimum of 5 months after the last dose of investigational product if male and 8 months after the last dose of investigational product if female.
8. Participation in other investigational studies during active treatment phase.
9. Other severe acute, chronic medical, psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the treating physician, would make the patient inappropriate for entry into this study.