Newly-diagnosed Intermediate/High Risk Pediatric B-cell ALL Protocol
CCCG-I/HR-ALL
Chinese Children's Cancer Group-2025 Protocol for Newly Diagnosed for Intermediate/High Risk Childhood B-cell ALL
1 other identifier
interventional
1,800
2 countries
26
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jan 2025
Longer than P75 for phase_2
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 20, 2024
CompletedStudy Start
First participant enrolled
January 3, 2025
CompletedFirst Posted
Study publicly available on registry
January 8, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2031
February 7, 2025
February 1, 2025
5 years
December 20, 2024
February 4, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
* 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.
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 (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.
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
- +2 more secondary outcomes
Other Outcomes (3)
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].
Up to five years
Cellular immune-status prior to Blinatumomab-HDMTX consolidation therapy
At the end of induction
Cellular immune functions after blinatumomab-HDMTX consolidation
Up to 2 years
Study Arms (3)
Group A
EXPERIMENTALAfter 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)
Group B
EXPERIMENTALAfter 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).
NonRandonmized Group
EXPERIMENTALPatients who will not be subjected to blinatomomab randomization, will received PVDL + Venetoclax + mini-hyperCVD as induction phase , subsequently receiving CAT as early intensification.
Interventions
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
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
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
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
Anhui Medical University Second Affiliated Hospital
Hefei, Anhui, China
Anhui Provincial Children's Hospital
Hefei, Anhui, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
Guangzhou Women and Children's Medical Center
Guangzhou, Guangdong, China
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, China
The People's Hospital of Guangxi Zhuang Autonomous Region
Nanning, Guangxi, China
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou, China
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Wuhan Children's Hospital
Wuhan, Hubei, China
Hunan Children's Hospital
Changsha, Hunan, China
Xiangya Hospital Central South University
Changsha, Hunan, China
Nanjing Children's Hospital Affiliated to Nanjing Medical University
Nanjing, Jiangsu, China
Children's Hospital of Soochow University
Suzhou, Jiangsu, China
Jiangxi Provincial Children's Hospital
Nanchang, Jiangxi, China
Qilu Hospital of Shandong University
Jinan, Shandong, China
Affiliated Hospital of Qingdao University
Qingdao, Shandong, China
Xi'an Northwest Women and Children Hospital
Xi’an, Shanxi, China
West China Second University Hospital, Sichuan University
Chengdu, Sichuan, China
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
Tianjin, Tianjin Municipality, 300020, China
Chongqing Medical University Affiliated Children's Hospital
Chongqing, China
Children's Hospital of Fudan University
Shanghai, China
Shanghai Children's Hospital
Shanghai, China
Shanghai Children's Medical Cener, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Shenzhen Children's Hospital
Shenzhen, China
Hong Kong Children's Hospital
Hong Kong, Hong Kong
Related Publications (10)
Middelmann HU, Sorba L, Hinkel V V, Horn K. Valence-band structure of alpha -Sn determined by angle-resolved photoemission. Phys Rev B Condens Matter. 1987 Jan 15;35(2):718-722. doi: 10.1103/physrevb.35.718. No abstract available.
PMID: 9941458BACKGROUNDToft N, Birgens H, Abrahamsson J, Griskevicius L, Hallbook H, Heyman M, Klausen TW, Jonsson OG, Palk K, Pruunsild K, Quist-Paulsen P, Vaitkeviciene G, Vettenranta K, Asberg A, Frandsen TL, Marquart HV, Madsen HO, Noren-Nystrom U, Schmiegelow K. Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia. Leukemia. 2018 Mar;32(3):606-615. doi: 10.1038/leu.2017.265. Epub 2017 Aug 18.
PMID: 28819280BACKGROUNDTeachey DT, Pui CH. Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. Lancet Oncol. 2019 Mar;20(3):e142-e154. doi: 10.1016/S1470-2045(19)30031-2.
PMID: 30842058BACKGROUNDPui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, Vora A, Baruchel A, Silverman LB, Schmiegelow K, Escherich G, Horibe K, Benoit YC, Izraeli S, Yeoh AE, Liang DC, Downing JR, Evans WE, Relling MV, Mullighan CG. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J Clin Oncol. 2015 Sep 20;33(27):2938-48. doi: 10.1200/JCO.2014.59.1636. Epub 2015 Aug 24.
PMID: 26304874BACKGROUNDPieters R, de Groot-Kruseman H, Van der Velden V, Fiocco M, van den Berg H, de Bont E, Egeler RM, Hoogerbrugge P, Kaspers G, Van der Schoot E, De Haas V, Van Dongen J. Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group. J Clin Oncol. 2016 Aug 1;34(22):2591-601. doi: 10.1200/JCO.2015.64.6364. Epub 2016 Jun 6.
PMID: 27269950BACKGROUNDMoricke A, Zimmermann M, Valsecchi MG, Stanulla M, Biondi A, Mann G, Locatelli F, Cazzaniga G, Niggli F, Arico M, Bartram CR, Attarbaschi A, Silvestri D, Beier R, Basso G, Ratei R, Kulozik AE, Lo Nigro L, Kremens B, Greiner J, Parasole R, Harbott J, Caruso R, von Stackelberg A, Barisone E, Rossig C, Conter V, Schrappe M. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood. 2016 Apr 28;127(17):2101-12. doi: 10.1182/blood-2015-09-670729. Epub 2016 Feb 17.
PMID: 26888258BACKGROUNDLeung 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. Epub 2023 Nov 25.
PMID: 38001171BACKGROUNDJeha 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. Epub 2019 Oct 28.
PMID: 31657981BACKGROUNDHunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012 May 10;30(14):1663-9. doi: 10.1200/JCO.2011.37.8018. Epub 2012 Mar 12.
PMID: 22412151BACKGROUNDEscherich G, Zimmermann M, Janka-Schaub G; CoALL study group. Doxorubicin or daunorubicin given upfront in a therapeutic window are equally effective in children with newly diagnosed acute lymphoblastic leukemia. A randomized comparison in trial CoALL 07-03. Pediatr Blood Cancer. 2013 Feb;60(2):254-7. doi: 10.1002/pbc.24273. Epub 2012 Sep 4.
PMID: 22948968BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Xiaofan Zhu, MD
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 20, 2024
First Posted
January 8, 2025
Study Start
January 3, 2025
Primary Completion (Estimated)
December 31, 2029
Study Completion (Estimated)
June 1, 2031
Last Updated
February 7, 2025
Record last verified: 2025-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- IPD will be made available upon publication of the primary trial results or after trial completion, whichever occurs first, starting on 2030, and will remain accessible for 5 years.
- Access Criteria
- Researchers, healthcare professionals who meet the criteria for access (e.g., academic researchers conducting secondary analyses or regulatory bodies reviewing safety data) will be able to request access to de-identified IPD and supporting information. Access will be facilitated through clinical trials.gov/emailing to PI, where users can submit a request and provide a research proposal. Data access will be granted after a formal review and approval process, subject to compliance with the data-sharing agreement and confidentiality terms.
1. Demographic Data: Age, sex, and other relevant baseline characteristics. 2. Treatment Information: Data on interventions received by participants, including dosage, treatment cycles, and duration. 3. Outcome Measures: Detailed information on primary and secondary outcome measures, such as response rates, survival rates, adverse events, and any the pre-specified endpoints. 4. Adverse Events: Data on all reported adverse events, including severity, duration, and outcome. 5. Laboratory Data: Results from laboratory tests, such as blood counts, biochemical markers, or molecular analysis. 6. Medical History: Pre-existing conditions, comorbidities, and prior treatments or interventions. 7. Vital Signs: relevant physiological data. 8. Efficacy and Safety Data: Any data relating to the efficacy (e.g., event-free survival) and safety (e.g., adverse effects) of the treatment.