Newly-diagnosed Pediatric T-cell ALL Protocol

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат Venetoclax
  All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy. For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in induction therapy. CAT will replace CAT+ during early intensification. Venetoclax will replace daunorubicin in interim therapy 2 and 4. 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.
• Препарат Dasatinib
  All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy. All non-ETP T-ALL patients will receive dasatinib after initial window phase in induction therapy. For non-ETP T-ALL patients with MRD \<0.01% on day 46, CAT will replace CAT+ during early intensification, and patients will be continuously subjected to dasatinib combined with chemotherapy during early intensification, interim tharapy, reinduction therapy and maintenance therapy. In maintenance therapy 2, the CTX+Ara-
• Препарат homoharringtonine
  All T-ALL patients will receive 8 mg/m2/day dexamethasone in induction therapy. All non-ETP T-ALL patients will receive dasatinib after initial window phase in induction therapy. For non-ETP T-ALL patients with MRD ≥0.01% on day 46，CAT+ will be replaced with randomized doses of homoharringtonine (HHT) during early intensification, and HHT will be administrated during reinduction therapy. In maintenance therapy 2, the CTX+Ara-C treatment cycles are reduced to 5, in order to minimize the impact of

Первичные конечные точки

• End-of-induction(EOI) measurable residual diseases (MRD)-negativity rate in patients with non-ETP T-ALL treated with dasatinib plus 4-drug induction compared to those treated with 4-drug induction in CCCG-ALL-2020 [Срок оценки: The expected study duration is approximately 5 years.]
• For non-ETP T-ALL patients with positive measurable residual diseases (MRD) on day 46, to compare MRD-negativity rate before consolidation between those receiving single agent homoharringtonine at dose of 1mg/m2 vs. 2mg/m2 for 7 days [Срок оценки: The expected study duration is approximately 5 years.]
• End of induction (EOI) measurable residual diseases (MRD)-negativity rate with venetoclax plus 3-drug induction, compared to those treated with 4-drug induction on CCCG-ALL-2020 in treating ETP/near-ETP T-ALL. [Срок оценки: The expected study duration is approximately 5 years.]
• In interim therapies 2 and 4, venetoclax replaced daunorubicin to evaluate whether this change could improve event-free survival compared to similar patients on CCCG-ALL-2020 in treating ETP/near-ETP T-ALL. [Срок оценки: The expected study duration is approximately 5 years.]

Вторичные конечные точки (4)

• Event-free survival (EFS) of patients treated with this therapy, in comparison to historical regimens. [Срок оценки: Approximately 6.5 years.]
• Overall survival (OS) of patients treated with this therapy, in comparison to historical regimens [Срок оценки: Approximately 6.5 years.]
• Cumulative incidence of relapse (CIR) of this therapy, in comparison to historical regimens. [Срок оценки: Approximately 6.5 years.]
• Incidence of Grade 4 Treatment-Emergent Adverse Events (TEAE) associated with venetoclax and homoharringtonine [Срок оценки: Up to 30 days after last dose of study treatment]

Критерии участия

Критерии включения

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

Критерии исключения

• B-ALL
• AML
• Acute leukemias of ambiguous lineage diagnosed according to WHO or EGIL criteria.
• ALL evolved from chronic myeloid leukemia (CML).
• Down's syndrome, or major congenital or hereditary disease with organ dysfunction
• Secondary leukemia
• Known underlying congenital immunodeficiency or metabolic disease
• Congenital heart disease with cardiac insufficiency.
• 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)
• 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.
• Severe malnutrition, active infections, heart failure, or chemotherapy intolerance.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 26 центров

• Anhui Medical University Second Affiliated Hospital — Хэфэй
• Anhui Provincial Children's Hospital — Хэфэй
• Chongqing Medical University Affiliated Children's Hospital — Чунцин
• Fujian Medical University Union Hospital — Фучжоу
• Guangzhou Women and Children's Medical Center — Гуанчжоу
• Nanfang Hospital, Southern Medical University — Гуанчжоу
• The People's Hospital of Guangxi Zhuang Autonomous Region — Nanning
• The Affiliated Hospital of Guizhou Medical University — Guiyang
• … и ещё 18 центров

Гонконг · 1 центр

• Hong Kong Children's Hospital — Гонконг

Публикации

• Teachey 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. C PMID 35271306
• Raetz 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/JC PMID 37487146
• Polonen 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, PMID 39143224
• He 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
• Simonin M, Vasseur L, Lengline E, Lhermitte L, Cabannes-Hamy A, Balsat M, Schmidt A, Dourthe ME, Touzart A, Graux C, Grardel N, Cayuela JM, Arnoux I, Gandemer V, Huguet F, Ducassou S, Lheritier V, Chalandon Y, Ifrah N, Dombret H, Macintyre E, Petit A, Rousselot P, Lambert J, Baruchel A, Boissel N, Asnafi V. NGS-based stratification refines the risk stratification in T-ALL and identifies a very-hig PMID 38848537
• Teachey DT, O'Connor D. How I treat newly diagnosed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in children. Blood. 2020 Jan 16;135(3):159-166. doi: 10.1182/blood.2019001557. PMID 31738819
• Summers RJ, Teachey DT, Hunger SP. How I treat ETP-ALL in children. Blood. 2025 Jan 2;145(1):43-52. doi: 10.1182/blood.2023023155. PMID 38364183
• Vora A, Goulden N, Mitchell C, Hancock J, Hough R, Rowntree C, Moorman AV, Wade R. Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2014 Jul;15(8):809-18. doi: 10.1016/S1470-2045(14)70243-8. PMID 24924991

Идентификаторы

NCT: NCT06855810 · IIT2025014

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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