Newly-diagnosed Intermediate/High Risk Pediatric B-cell ALL Protocol

Официальное название

Chinese Children's Cancer Group-2025 Protocol for Newly Diagnosed for Intermediate/High Risk Childhood B-cell ALL

Обзор

Building upon the results from the CCCG-ALL-2015, CCCG-ALL-2020 multicenter study cohort, concurrent research findings, and the latest clinical trials, the CCCG-ALL-2025 I/HR-B-ALL is thus developed to further improve the event-free survival (EFS), and overall survival (OS), and quality of life (QoL) of children with intermediate- and high- risk B-cell childhood acute lymphoblastic leukaemia (I/HR-B-ALL), while decreasing adverse reactions and transplantation rates. This trial primarily aims to explore: 1. The efficacy of two randomized Blinatumomab application scheme on I/HR-ALL as determined by MRD negatvitiy rate. 2. The efficacy of modified mini-hyperCVD + Venetoclax in I/HR-ALL cannot afford blinatumomab, in contrast to historical control as determined by MRD negatvitiy rate.

Подробное описание

The study shown above will lead to the following revisions to the CCCG-ALL2025 I/HR-B-ALL plan, which will be based on the CCCG-ALL2020 plan.

1. After the induction remission phase, all I/HR-B-ALL patients can afford blinatumomab will participate in a blinatumomab+HDMTX randomized controlled trial as consolidation. 2. For patients cannot afford blinatumomab will be treated with venetoclax + modified mini-hyperCVD during the induction phase, then subsequently with CAT as consolidation phase. CAT will removed from induction phase. 3. For patients who received blinatumomab randomization, the CAT+ course was canceled. 4. All patients will continued with 6 cycles of alternated 5-day venetoclax or Dauno-based CCCG-2020 continuous therapy regimen. 5. Adding IgH rearrangement NGS MRD as an evaluation indicator. 6. Adding pharmacotyping study for I/HR B-ALL. 7. Three more bone marrow punctures and IT will be added with the aims to evaluate the CR rate with deepen remission during or after consolidation.

Вмешательства

• Препарат Blinatumomab (Group A)
  For Group A I/HR-ALL patients after induction remission phase, continuous 28 days' blinatumomab followed by 3 cycles of high-dose methotrexate (HDMTX) will be applied, subsequently followed by interim continuation, late intensification, and maintenance therapy
• Препарат Venetoclax (nonRand Group)
  For I/HR patients non eligible for blinatumomab randomization, venetoclax+ mini-hyperCVD will be applied after PVDL induction, subsequently followed by CAT as intensification, interim continuation, late intensification, and maintenance therapy
• Препарат Blinatumomab (Group B)
  For Group B I/HR-ALL patients after induction remission phase: a two 14-day cycles of blinatumomab, alternating with three cycles of HDMTX will be applied, subsequently followed interim continuation, late intensification, and maintenance therapy

Первичные конечные точки

• To investigate if Group B[2*(14-day blinatumomab + HDMTX*2)] can result in noninferior event-free survival (EFS) compared to Group A [28-day blinatumomab + HDMTX*4 [Срок оценки: Based on the above analysis in this study the investigators will randomize 1800 patients. The analysis will start1.5 years after the last patient is randomized. The expected study duration is approximately 6.5 years.]

Вторичные конечные точки (7)

• Event-free survival (EFS) in the two randomized arms [2*(14-day blinatumomab + HDMTX*2)] and [28-day blinatumomab + HDMTX*4], in contrast to historical regimens. [Срок оценки: Up to 5 years for every enrolled case]
• Cumulative incidence of relapse (CIR) in the two randomized arms [2*(14-day blinatumomab + HDMTX*2)] and [28-day blinatumomab + HDMTX*4], in contrast to historical regimen. [Срок оценки: Up to 5 years for every enrolled case]
• Overall survival (OS) in the two randomized arms [2*(14-day blinatumomab + HDMTX*2)] and [28-day blinatumomab + HDMTX*4], in contrast to historical regimens. [Срок оценки: Up to 5 years for every enrolled case]
• EFS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy. [Срок оценки: Up to 5 years for every enrolled case]
• CIR in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy. [Срок оценки: Up to five years for every enrolled case]
• OS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy. [Срок оценки: Up to five years for every enrolled case]
• To compare grade 3 or higher adverse effects (AEs; CTCAE v5.0) and estimate their cumulative incidences [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 B-ALL by immunophenotyping.

Критерии исключения

• Low-risk ALL
• sIgM+
• 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)

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

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
• 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
• Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology — Ухань
• … и ещё 18 центров

Гонконг · 1 центр

• Hong Kong Children's Hospital — Гонконг

Публикации

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• Leung KT, Cai J, Liu Y, Chan KYY, Shao J, Yang H, Hu Q, Xue Y, Wu X, Guo X, Zhai X, Wang N, Li X, Tian X, Li Z, Xue N, Guo Y, Wang L, Zou Y, Xiao P, He Y, Jin R, Tang J, Yang JJ, Shen S, Pui CH, Li CK. Prognostic implications of CD9 in childhood acute lymphoblastic leukemia: insights from a nationwide multicenter study in China. Leukemia. 2024 Feb;38(2):250-257. doi: 10.1038/s41375-023-02089-3. Ep PMID 38001171
• Jeha S, Pei D, Choi J, Cheng C, Sandlund JT, Coustan-Smith E, Campana D, Inaba H, Rubnitz JE, Ribeiro RC, Gruber TA, Raimondi SC, Khan RB, Yang JJ, Mullighan CG, Downing JR, Evans WE, Relling MV, Pui CH. Improved CNS Control of Childhood Acute Lymphoblastic Leukemia Without Cranial Irradiation: St Jude Total Therapy Study 16. J Clin Oncol. 2019 Dec 10;37(35):3377-3391. doi: 10.1200/JCO.19.01692. E PMID 31657981

Идентификаторы

NCT: NCT06764238 · IIT2024068

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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