A Single-center, Prospective, Exploratory Clinical Study

A Single-Center, Prospective, Exploratory Clinical Study of the Lishatoclax Combination Regimen in Adult Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

This study is designed as a prospective, single-arm, exploratory clinical trial based on lishatoclax, enrolling three independent cohorts of patients with Philadelphia chromosome-positive (Ph⁺) ALL, Philadelphia chromosome-negative (Ph-) ALL, and T-cell ALL (T-ALL). By investigating the combination of lishatoclax with established standard chemotherapy, targeted agents (e.g., tyrosine kinase inhibitors, TKIs), or immunotherapies, this study aims to further improve the remission rates across all ALL subtypes, and to develop a more effective and less toxic novel therapeutic strategy for ALL, thereby addressing the unmet clinical needs in current practice.

Inclusion Criteria:

1. Newly diagnosed acute lymphoblastic leukemia (ALL) confirmed by bone marrow morphology, immunophenotyping, cytogenetics, and molecular biology according to the WHO 2022 classification criteria.

2. Age ≥ 18 years, male or female.

3. Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2.

4. Life expectancy ≥ 3 months.

5. Males and females of childbearing potential who agree to use effective contraceptive measures.

6. Adequate organ function as defined by the following laboratory parameters:

   Total bilirubin ≤ 1.5 × upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN; Serum creatinine < 1.5 × ULN; Serum amylase ≤ 1.5 × ULN; Creatine kinase-MB (CK-MB) ≤ 2 × ULN.

7. Cardiac ejection fraction > 45% as determined by multigated acquisition (MUGA) scan.

8. Voluntary participation in this clinical trial, with an understanding of the study procedures and the ability to provide written informed consent.

Exclusion Criteria:

1. Diagnosis of mixed-phenotype acute leukemia (MPAL) or Burkitt lymphoma/leukemia according to the WHO 2008 classification criteria for tumors of hematopoietic and lymphoid tissues.
2. Concurrent severe and/or uncontrolled underlying diseases, including but not limited to: other malignancies requiring concurrent treatment, acute or chronic hepatitis, severe pancreatic or renal disease, or other life-threatening underlying conditions; presence of severe active infections (e.g., sepsis, active tuberculosis, uncontrolled pneumonia, etc.).
3. Pregnant or lactating women.
4. Positive test for anti-HIV antibodies.
5. Psychiatric disorders that may interfere with the patient's ability to complete the study treatment or provide informed consent.
6. Any condition deemed by the investigator to make the patient unsuitable for enrollment.
7. Inability to swallow capsules or tablets, or presence of gastrointestinal disorders significantly affecting gastrointestinal function and/or inhibiting small intestinal absorption (including malabsorption syndrome, small bowel resection, or poorly controlled inflammatory bowel disease).
8. Known hypersensitivity to the study drug or any of its excipients.