Clinical trial NCT06764238: Newly-diagnosed Intermediate/High Risk Pediatric B-cell ALL Protocol
Official title: Chinese Children's Cancer Group-2025 Protocol for Newly Diagnosed for Intermediate/High Risk Childhood B-cell ALL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acute Lymphoblastic Leukemia ALL
Childhood Leukemia, Acute Lymphoblastic
B Cell Acute Lymphoblastic Leukemia (B-ALL)
Keywords: blinatimomab
venetoclax
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2025-01-08
Enrollment: 1800
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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 B-ALL by immunophenotyping.

Exclusion Criteria:

1. Low-risk ALL
2. sIgM+
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)

Primary outcomes:
measure: 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
timeFrame: 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.
Secondary outcomes:
measure: 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.
timeFrame: Up to 5 years for every enrolled case
measure: 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.
timeFrame: Up to 5 years for every enrolled case
measure: 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.
timeFrame: Up to 5 years for every enrolled case
measure: EFS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.
timeFrame: Up to 5 years for every enrolled case
measure: CIR in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.
timeFrame: Up to five years for every enrolled case
measure: OS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.
timeFrame: Up to five years for every enrolled case
measure: To compare grade 3 or higher adverse effects (AEs; CTCAE v5.0) and estimate their cumulative incidences
timeFrame: Up to 30 days after last dose of study treatment
Other outcomes:
measure: measurable residual diseases (MRD) positivity by next-generation sequencing of immunoglobulin gene(IgH NGS) after blinatumomab-HDMTX therapy between the two randomized arms [2*(14-day blinatumomab + HDMTX*2)] and [28-day blinatumomab + HDMTX*4].
timeFrame: Up to five years
measure: Cellular immune-status prior to Blinatumomab-HDMTX consolidation therapy
timeFrame: At the end of induction
measure: Cellular immune functions after blinatumomab-HDMTX consolidation
timeFrame: Up to 2 years
Locations:
city: Hefei
country: China
facility: Anhui Medical University Second Affiliated Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Children's Hospital
state: Anhui
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Guangzhou Women and Children's Medical Center
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Guiyang
country: China
facility: The Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Wuhan Children's Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Children's Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Nanjing
country: China
facility: Nanjing Children's Hospital Affiliated to Nanjing Medical University
state: Jiangsu
city: Suzhou
country: China
facility: Children's Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial Children's Hospital
state: Jiangxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Qingdao
country: China
facility: Affiliated Hospital of Qingdao University
state: Shandong
city: Xi'an
country: China
facility: Xi'an Northwest Women and Children Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Second University Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
state: Tianjin
city: Chongqing
country: China
facility: Chongqing Medical University Affiliated Children's Hospital
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
city: Shanghai
country: China
facility: Shanghai Children's Hospital
city: Shanghai
country: China
facility: Shanghai Children's Medical Cener, Shanghai Jiao Tong University School of Medicine
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
city: Hong Kong
country: Hong Kong
facility: Hong Kong Children's Hospital
Study officials:
affiliation: Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
name: Xiaofan Zhu, MD
role: PRINCIPAL_INVESTIGATOR
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