Newly-diagnosed Pediatric T-cell ALL Protocol

Chinese Children's Cancer Group T-cell Acute Lymphoblastic Leukemia -2025 Project

This is a prospective, multicenter study conducted within the Chinese Children's Cancer Group (CCCG). The study aims to evaluate whether the addition of three novel agents, dasatinib, venetoclax and homoharringtonine, can improve the minimal residual disease (MRD)-negative remission rate, enhance event-free survival (EFS), and reduce the cumulative incidence of relapse (CIR) in pediatric patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL).

The CCCG-T-ALL-2025 protocol will be modified as following based on the above analysis of the CCCG-ALL-2020 protocol.

1. All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy.
2. All non-ETP T-ALL patients will receive dasatinib after initial window phase in induction therapy.
3. non-ETP T-ALL patients with MRD ≥ 0.01% on day 46 will be stratified and randomized to receive different doses of homoharringtonine during early intensification.
4. For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in induction therapy.
5. For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in interim therapy 2 and 4.
6. CAT will replace CAT+ during early intensification, and will be administrated to all ETP/near-ETP patients, as well as non-ETP patients with MRD< 0.01% on day 46.

2.11.7 In maintenance therapy 2, the CTX+Ara-C treatment cycles are reduced to 5, in order to minimize the impact of alkylating agents on fertility.

2.11.8 Add drug sensitivity testing for T-ALL.

Inclusion Criteria:

1. Age older than 1 month to younger than 18 years.
2. Diagnosis of acute lymphoblastic leukemia by bone marrow morphology.
3. Diagnosis of T-ALL by immunophenotyping.

Exclusion Criteria:

1. B-ALL
2. AML
3. Acute leukemias of ambiguous lineage diagnosed according to WHO or EGIL criteria.
4. ALL evolved from chronic myeloid leukemia (CML).
5. Down's syndrome, or major congenital or hereditary disease with organ dysfunction
6. Secondary leukemia
7. Known underlying congenital immunodeficiency or metabolic disease
8. Congenital heart disease with cardiac insufficiency.
9. Treated with glucocorticoids for ≥14 days, or ABL kinase inhibitors for > 7 days within one month before enrollment, or any chemotherapy or radiotherapy within 3 months before enrollment (except for emergency radiotherapy to relieve airway compression)
10. Any significant comorbidities or psychiatric disorders that may impact patient safety, compliance, informed consent, study participation, follow-up, or the interpretation of study results. In such cases, all participating sites must report directly to the PI to determine whether the patient meets exclusion criteria.
11. Severe malnutrition, active infections, heart failure, or chemotherapy intolerance.