Newly-diagnosed Pediatric T-cell ALL Protocol

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).

Sex

All

Minimum age

1 Month

Maximum age

18 Years

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.

• BACKGROUNDTeachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ, Hermiston ML, Annett RD, Archer JH, Asselin BL, August KJ, Cho SY, Dunsmore KP, Fisher BT, Freedman JL, Galardy PJ, Harker-Murray P, Horton TM, Jaju AI, Lam A, Messinger YH, Miles RR, Okada M, Patel SI, Schafer ES, Schechter T, Singh N, Steele AC, Sulis ML, Vargas SL, Winter SS, Wood C, Zweidler-McKay P, Bollard CM, Loh ML, Hunger SP, Raetz EA. Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma. J Clin Oncol. 2022 Jul 1;40(19):2106-2118. doi: 10.1200/JCO.21.02678. Epub 2022 Mar 10. PMID 35271306
• BACKGROUNDRaetz EA, Rebora P, Conter V, Schrappe M, Devidas M, Escherich G, Imai C, De Moerloose B, Schmiegelow K, Burns MA, Elitzur S, Pieters R, Attarbaschi A, Yeoh A, Pui CH, Stary J, Cario G, Bodmer N, Moorman AV, Buldini B, Vora A, Valsecchi MG. Outcome for Children and Young Adults With T-Cell ALL and Induction Failure in Contemporary Trials. J Clin Oncol. 2023 Nov 10;41(32):5025-5034. doi: 10.1200/JCO.23.00088. Epub 2023 Jul 24. PMID 37487146
• BACKGROUNDPolonen P, Di Giacomo D, Seffernick AE, Elsayed A, Kimura S, Benini F, Montefiori LE, Wood BL, Xu J, Chen C, Cheng Z, Newman H, Myers J, Iacobucci I, Li E, Sussman J, Hedges D, Hui Y, Diorio C, Uppuluri L, Frank D, Fan Y, Chang Y, Meshinchi S, Ries R, Shraim R, Li A, Bernt KM, Devidas M, Winter SS, Dunsmore KP, Inaba H, Carroll WL, Ramirez NC, Phillips AH, Kriwacki RW, Yang JJ, Vincent TL, Zhao Y, Ghate PS, Wang J, Reilly C, Zhou X, Sanders MA, Takita J, Kato M, Takasugi N, Chang BH, Press RD, Loh M, Rampersaud E, Raetz E, Hunger SP, Tan K, Chang TC, Wu G, Pounds SB, Mullighan CG, Teachey DT. The genomic basis of childhood T-lineage acute lymphoblastic leukaemia. Nature. 2024 Aug;632(8027):1082-1091. doi: 10.1038/s41586-024-07807-0. Epub 2024 Aug 14. PMID 39143224
• BACKGROUNDHe Y, Zhang J, Zhang Y, Hu Z, Wang P, Gan W, Xie S, Qian M, Pui CH, Jiang H, Zhu X, Zhang H, Zhang W. Dasatinib-therapy induced sustained remission in a child with refractory TCF7-SPI1 T-cell acute lymphoblastic leukemia. Pediatr Blood Cancer. 2022 Aug;69(8):e29724. doi: 10.1002/pbc.29724. Epub 2022 Apr 20. PMID 35441457