Chinese Children's Cancer Group-2025 Protocol for Newly Diagnosed for Intermediate/High Risk Childhood B-cell ALL
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 1,800
- 试验地点
- 27
- 主要终点
- 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
研究概览
简要总结
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:
- The efficacy of two randomized Blinatumomab application scheme on I/HR-ALL as determined by MRD negatvitiy rate.
- 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.
详细描述
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.
- 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.
- 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.
- For patients who received blinatumomab randomization, the CAT+ course was canceled.
- All patients will continued with 6 cycles of alternated 5-day venetoclax or Dauno-based CCCG-2020 continuous therapy regimen.
- Adding IgH rearrangement NGS MRD as an evaluation indicator.
- Adding pharmacotyping study for I/HR B-ALL.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Low-risk ALL
- •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)
研究组 & 干预措施
Group A
After PVDL+CAT induction remission phase, patients randomized to Group A will be subjected to consolidation phase with continuous 28 days' blinatumomab followed by 3 cycles of high-dose methotrexate (HDMTX)
干预措施: Blinatumomab (Group A) (Drug)
Group B
After PVDL+CAT induction remission phase, patients randomized to Group B will be subjected to consolidation phase with two 14-day cycles of blinatumomab, alternating with 3 cycles of high-dose methotrexate (HDMTX).
干预措施: Blinatumomab (Group B) (Drug)
NonRandonmized Group
Patients who will not be subjected to blinatomomab randomization, will received PVDL + Venetoclax + mini-hyperCVD as induction phase , subsequently receiving CAT as early intensification.
干预措施: Venetoclax (nonRand Group) (Drug)
结局指标
主要结局
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
时间窗: 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.
* The randomization is stratified by hospitals and status of flow-cytometry MRD (positive or negative) immediately prior to the blinatumomab-HDMTX treatment. * Kaplan-Meier (KM) estimates of each EFS function will be computed along with standard error by the default procedure in R. To test noninferiority the investigators consider a noninferiority margin of 0.04 for 5-year EFS as clinically meaningful. * Assume the EFS in the control group (Arm A) to be the same as the provisional I/HR in the CCCG-ALL2020 trial (preliminary data above), with the 1-year and 3-year EFS possibly 0.837 and 0.768 respectively. A simulation study with 10,000 rounds shows that by randomizing 1800 patients and 1.5 years of follow up, the above decision rule of declaring noninferiority has well controlled probabilities of false positive and false negative errors.
次要结局
- 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.(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.(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.(Up to 5 years for every enrolled case)
- EFS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.(Up to 5 years for every enrolled case)
- CIR in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.(Up to five years for every enrolled case)
- OS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.(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(Up to 30 days after last dose of study treatment)