Chinese Children's Cancer Group T-cell Acute Lymphoblastic Leukemia -2025 Project
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 610
- 试验地点
- 27
- 主要终点
- 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
研究概览
简要总结
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).
详细描述
The CCCG-T-ALL-2025 protocol will be modified as following based on the above analysis of the CCCG-ALL-2020 protocol.
- 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.
- 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.
- For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in induction therapy.
- For all ETP/near-ETP T-ALL patients, venetoclax will replace daunorubicin in interim therapy 2 and 4.
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 T-ALL by immunophenotyping.
排除标准
- •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.
研究组 & 干预措施
(near)ETP-ALL
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.
干预措施: Venetoclax (Drug)
nonETP-TALL-Das Group
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-C treatment cycles are reduced to 5, in order to minimize the impact of alkylating agents on fertility.
干预措施: Dasatinib (Drug)
nonETP-TALL-HHT Group
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 alkylating agents on fertility.
干预措施: homoharringtonine (Drug)
结局指标
主要结局
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
时间窗: The expected study duration is approximately 5 years.
For this objective a one-sided comparison of probabilities (proportions) will be made. Let p1 and p2 be the probability of aciieving negative EOI MRD on the CCCG-ALL-2020 (historical control) and the current study respectively, then the one-sided alternative hypothesis H0: p2=p1 vs. H1: p2\>p1 will be tested. The procedure of two-sample comparison of proportions with the Z-statistic (Normal approximation) will be applied. The current CCCG-ALL2020 data show that among 573 evaluable patients 510 (89%) achaived negative EOI MRD. Benchmarking on these as historical data, a total sample size of n=550 and interim sample size n1=300 provides sufficient popwer for the planned analyses outlined above if the true MRD negativity probability is 0.92 or higher, as shown in the table below. An interim analysis at n1=300 evaluable patients will be conducted for possible abstract submission or publication.
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
时间窗: The expected study duration is approximately 5 years.
The comparison will be condicted by testing the two-sided hypothesis H0: p1=p2 vs. H1: p1≠p2, using the Z test (normal approximation) at alpha=0.10 level. The investigators anticipate approximately 40 patients available to be randomized. The participants will be randomized at 1:1 ratio into the two treatment arms, with 20 patients per arm. Stratified block-wise randomization will be applied with block size of 4. The randomization will be stratified by the EOI MRD level as \<1% and \>=1%.
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.
时间窗: The expected study duration is approximately 5 years.
The investigators anticipate at least 60 evaluable ETP participants. The analysis will be conducted by testing H0: p2=p1 vs. H1: p2\>p1, where p1, p2 are MRD-negative probabilities in the CCCG-ALL-2020 and the current study respectively. The Z-statistic (normal approximation) based procedure will be applied.
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.
时间窗: The expected study duration is approximately 5 years.
The investigators anticipate at least 60 evaluable participants. The event-free survival function will be estimated by the Kaplan-Meier method. Comparison will be conducted using the two-sided log-rank test.
次要结局
- Event-free survival (EFS) of patients treated with this therapy, in comparison to historical regimens.(Approximately 6.5 years.)
- Overall survival (OS) of patients treated with this therapy, in comparison to historical regimens(Approximately 6.5 years.)
- Cumulative incidence of relapse (CIR) of this therapy, in comparison to historical regimens.(Approximately 6.5 years.)
- Incidence of Grade 4 Treatment-Emergent Adverse Events (TEAE) associated with venetoclax and homoharringtonine(Up to 30 days after last dose of study treatment)