Acute Lymphoblastic Leukemia ALLPhase 2/3CCCG-I/HR-ALLNCT06764238

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

A Phase 2/3 study testing Blinatumomab (Group A), Venetoclax (nonRand Group) and Blinatumomab (Group B) in people with Acute Lymphoblastic Leukemia ALL and Childhood Leukemia, Acute Lymphoblastic, run by Institute of Hematology & Blood Diseases Hospital, China at 27 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

Search all trials

Trial summary

Who is it for?: Ages 1 month to 18 years
Conditions the study is for: Acute Lymphoblastic Leukemia ALL, Childhood Leukemia, Acute Lymphoblastic, B Cell Acute Lymphoblastic Leukemia (B-ALL)
What is being tested?: Blinatumomab (Group A), Venetoclax (nonRand Group) and Blinatumomab (Group B)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,800 participants
Where: 27 sitesin 2 countries
Study dates: 3 Jan 2025to Jun 2031
Phase: Phase 2/3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 month to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

Who cannot join

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

Show all 9Show fewer

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)

Trial locations and contacts

27 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Jingliao Zhang, MD contact

+86 22 23909196

zhangjingliao@ihcams.ac.cn

Xiaofan Zhu, MD contact

+ 86 22 23909001

xfzhu@ihcams.ac.cn

Country

City, postcode or hospital

Sites recruiting now only

27 sites in 2 countries

China26 sites, 26 recruiting

Hunan Children's Hospital
Changsha, Hunan
Wenyong Kuang, PhD, 0731-85356114, kathy5460@sina.com
Not yet recruiting
The Third Xiangya Hospital of the Central South University
Changsha, Hunan
Minghua Yang, MD, 0731-88618576, yangminghua@csu.edu.cn
Not yet recruiting
Xiangya Hospital Central South University
Changsha, Hunan
Liangchun Yang, MD, 0731-89753999, yangliangchung@163.com
Not yet recruiting
West China Second University Hospital, Sichuan University
Chengdu, Sichuan
Ju Gao, MD, 028-85503960, tree20002005@163.com
Not yet recruiting
Chongqing Medical University Affiliated Children's Hospital
Chongqing
Jie Yu, MD, 023-63632756, 1808106657@qq.com
Not yet recruiting
Fujian Medical University Union Hospital
Fuzhou, Fujian
Jian Li, MD, 0591-83357896, 1354113723@qq.com
Not yet recruiting
Guangzhou Women and Children's Medical Center
Guangzhou, Guangdong
Hua Jiang, MD, 020-81886332, jiang_hua18@sina.cn
Not yet recruiting
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong
Xuedong Wu, MD, 020-61641114, xuedongwu@163.com
Not yet recruiting
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou
Jiao Jin, MD, 0851-86772025, jinjiao999@gmc.edu.cn
Not yet recruiting
Anhui Medical University Second Affiliated Hospital
Hefei, Anhui
Ningling Wang, MD, 0551-63869302, zwnltt@126.com
Not yet recruiting
Anhui Provincial Children's Hospital
Hefei, Anhui
Xuhan Zhang, PhD, 0551-62284005, zmsun_vip@163.com
Not yet recruiting
Qilu Hospital of Shandong University
Jinan, Shandong
Xiuli Ju, MD, 0531-82169114, shellysdcn@hotmail.com
Not yet recruiting
Jiangxi Provincial Children's Hospital
Nanchang, Jiangxi
Fei He, MD, 0791-86802382, hefei1944@163.com
Not yet recruiting
Nanjing Children's Hospital Affiliated to Nanjing Medical University
Nanjing, Jiangsu
Yongjun Fang, MD, 025-83117500, fyj322@189.cn
Not yet recruiting
The People's Hospital of Guangxi Zhuang Autonomous Region
Nanning, Guangxi
Yan Dai, MD, 0771-2635268, 3677458@qq.com
Not yet recruiting
Affiliated Hospital of Qingdao University
Qingdao, Shandong
Lingzhen Wang, PhD, 0532-96166, hopewang2006@163.com
Not yet recruiting
Children's Hospital of Fudan University
Shanghai
Xiaowen Zhai, MD, 021-64931990, zhaixiaowendy@163.com
Not yet recruiting
Shanghai Children's Hospital
Shanghai
Hui Jiang, MD, 021-62474880, jhui0111@126.com
Not yet recruiting
Shanghai Children's Medical Cener, Shanghai Jiao Tong University School of Medicine
Shanghai
Shuhong Shen, MD, 021-3862616, shenshuhong@scmc.com.cn
Not yet recruiting
Shenzhen Children's Hospital
Shenzhen, Shenzhen
Sixi Liu, MD, 83936101, tiger647@126.com
Not yet recruiting
Children's Hospital of Soochow University
Suzhou, Jiangsu
Shaoyan Hu, MD, 0512-80695102, hsyl39@126.com
Not yet recruiting
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
Tianjin, Tianjin Municipality, 300020
Xiaofan Zhu, MD, +86 22 23909001, xfzhu@ihcams.ac.cn
Xiaofan Zhu, MD
Recruiting
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei
Aiguo Liu, PhD, 027-83663131, aiguoliu309@163.com
Not yet recruiting
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei
Xiaoyan Wu, PhD, 027-85726114, xiaoyanw8016@163.com
Not yet recruiting
Wuhan Children's Hospital
Wuhan, Hubei
Hao Xiong, MD, 13006107360, 22587481@qq.com
Not yet recruiting
Xi'an Northwest Women and Children Hospital
Xi’an, Shanxi
Jian Zhang, MD, 029-89550001, kailipan@fmmu.edu.cn
Not yet recruiting

Other trials in China

Hong Kong1 site, 1 recruiting

Hong Kong Children's Hospital
Hong Kong
Chi-kong Li, MD, (852) 3505-2849, ckli@cuhk.edu.hk
Not yet recruiting

Other trials in Hong Kong

About this study

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

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.

Read the 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.

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.

Conditions: Acute Lymphoblastic Leukemia ALL, Childhood Leukemia, Acute Lymphoblastic, B Cell Acute Lymphoblastic Leukemia (B-ALL)
Being tested: Blinatumomab (Group A), Venetoclax (nonRand Group), Blinatumomab (Group B)
Keywords: blinatimomab, venetoclax
Medical subject headings: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Blinatumomab (Group A)Drug
Also called high-dose methotrexate
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
Venetoclax (nonRand Group)Drug
Also called cyclophosphamide, vincristine, dexamethasone
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
Blinatumomab (Group B)Drug
Also called high-dose methotrexate
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

Study groups in NCT06764238
Study group	Role	What they receive
Group A	Experimental	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) Receives: Drug: Blinatumomab (Group A)
Group B	Experimental	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). Receives: Drug: Blinatumomab (Group B)
NonRandonmized Group	Experimental	Patients who will not be subjected to blinatomomab randomization, will received PVDL + Venetoclax + mini-hyperCVD as induction phase , subsequently receiving CAT as early intensification. Receives: Drug: Venetoclax (nonRand Group)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
EFS functions will be estimated using the Kaplan-Meier estimator of survival functions along with 95% confidence interval at 5 year. Standard error will be estimated using the default procedure in R. Follow up of the historical comparison cohort (CCCG-ALL-2020 and 2015) will continue during the course of the current trial. Comparisons of EFS will be performed using two-sided log-rank test. Multivariable regression modeling including trial (CCCGALL-2025 vs. 2020 or 2015) and other known prognostic factors as main effects may also be performed, using the Cox models.
Measured: 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.
CIR functions of relapse will be estimated by the Kalbafleisch-Prentice method. Follow up of the historical comparison cohort (CCCG-ALL-2020 and 2015) will continue during the course of the current trial. Comparisons of CIR will be performed by Gray's test. Multivariable regression modeling including trial (CCCGALL-2025 vs. 2020 or 2015) and other known prognostic factors as main effects may also be performed, using the Fine-Gray models.
Measured: 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.
OS functions will be estimated using the Kaplan-Meier estimator of survival functions along with 95% confidence interval at 5 year. Standard error will be estimated using the default procedure in R. Follow up of the historical comparison cohort (CCCG-ALL-2020 and 2015) will continue during the course of the current trial. Comparisons of OS will be performed using two-sided log-rank test. Multivariable regression modeling including trial (CCCGALL-2025 vs. 2020 or 2015) and other known prognostic factors as main effects may also be performed, using the Cox models.
Measured: Up to 5 years for every enrolled case
EFS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.
EFS functions will be estimated using the Kaplan-Meier estimator of survival functions along with 95% confidence interval at 5 year. Standard error will be estimated using the default procedure in R. Follow up of the historical comparison cohort (CCCG-ALL-2020 and 2015) will continue during the course of the current trial. Comparisons of EFS will be performed using two-sided log-rank test.Multivariable regression modeling including trial (CCCGALL-2025 vs. 2020 or 2015) and other known prognostic factors as main effects may also be performed, using the Cox models.
Measured: Up to 5 years for every enrolled case
CIR in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.
CIR functions of relapse will be estimated by the Kalbafleisch-Prentice method. Follow up of the historical comparison cohort (CCCG-ALL-2020 and 2015) will continue during the course of the current trial. Comparisons of CIR will be performed by Gray's test. Multivariable regression modeling including trial (CCCGALL-2025 vs. 2020 or 2015) and other known prognostic factors as main effects may also be performed, using the Fine-Gray models.
Measured: Up to five years for every enrolled case
OS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.
OS will be estimated using the Kaplan-Meier estimator of survival functions along with 95% confidence interval at 5 year. Standard error will be estimated using the default procedure in R. Follow up of the historical comparison cohort (CCCG-ALL-2020 and 2015) will continue during the course of the current trial. Comparisons of OS will be performed using two-sided log-rank test. Multivariable regression modeling including trial (CCCGALL-2025 vs. 2020 or 2015) and other known prognostic factors as main effects may also be performed, using the Cox models.
Measured: 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
Proportions of grade-3 or higher AEs in each treatment phase will be estimated by the sample proportions along with exact 95% confidence intervals. Cumulative incidences of various grade-3 or higher AEs throughout therapy will be estimated by the Kalbafleisch-Prentice method; death, relapse and other events rendering off therapy before completion are regarded as competing risks.
Measured: Up to 30 days after last dose of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Jan 2025Jun 2031

First posted8 Jan 2025
Study start3 Jan 2025
Primary completion31 Dec 2029 (estimated)
Study completionJun 2031 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (10)Papers the sponsor has linked to this study.
Other trials for Acute Lymphoblastic Leukemia ALLStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 1,800 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06764238
Sponsor's protocol ID: IIT2024068
Acronym: CCCG-I/HR-ALL
Status last verified: Feb 2026
First submitted: 20 Dec 2024
Last updated: 23 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: 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.

Publications

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.
PubMed 9941458
Toft 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.
PubMed 28819280
Teachey 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.
PubMed 30842058
Pui 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.
PubMed 26304874
Pieters 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.
PubMed 27269950
Moricke 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.
PubMed 26888258
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. Epub 2023 Nov 25.
PubMed 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. Epub 2019 Oct 28.
PubMed 31657981
Hunger 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.
PubMed 22412151
Escherich 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.
PubMed 22948968

Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Chinese Children's Cancer Group-2025 Protocol for Newly Diagnosed for Intermediate/High Risk Childhood B-cell ALL
ClinicalTrials.gov ID: NCT06764238
Acronym / sponsor ID: CCCG-I/HR-ALL / IIT2024068
Conditions: Acute Lymphoblastic Leukemia ALL, Childhood Leukemia, Acute Lymphoblastic, B Cell Acute Lymphoblastic Leukemia (B-ALL)
Keywords: blinatimomab, venetoclax
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 1,800 participants (estimated)
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
Study start: 3 Jan 2025 (actual)
Primary completion: 31 Dec 2029 (estimated)
Study completion: Jun 2031 (estimated)
First posted: 8 Jan 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

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.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Group A	Experimental	Drug: Blinatumomab (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)
Group B	Experimental	Drug: Blinatumomab (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).
NonRandonmized Group	Experimental	Drug: Venetoclax (nonRand 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.

Who may qualify

Ages: 1 month to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Blinatumomab (Group A)Also: high-dose methotrexateFor 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	Drug	Group A
Venetoclax (nonRand Group)Also: cyclophosphamide, vincristine, dexamethasoneFor 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	Drug	NonRandonmized Group
Blinatumomab (Group B)Also: high-dose methotrexateFor 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	Drug	Group B

Primary outcome

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
Time frame: 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.

7 secondary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 5 years for every enrolled case
EFS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.
Time frame: Up to 5 years for every enrolled case
CIR in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.
Time frame: Up to five years for every enrolled case
OS in patients who receive 6 alternated venetoclax/Daunorubincin courses of interim continuation therapy.
Time frame: 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
Time frame: Up to 30 days after last dose of study treatment

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
Background: PubMed 9941458Middelmann 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.
Background: PubMed 28819280Toft 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.
Background: PubMed 30842058Teachey 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.
Background: PubMed 26304874Pui 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.
Background: PubMed 27269950Pieters 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.
Background: PubMed 26888258Moricke 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.
Background: PubMed 38001171Leung 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.
Background: PubMed 31657981Jeha 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.
Background: PubMed 22412151Hunger 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.
Background: PubMed 22948968Escherich 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.
data collecting websiteLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Jingliao Zhang, MD contact

+86 22 23909196

zhangjingliao@ihcams.ac.cn

Xiaofan Zhu, MD contact

+ 86 22 23909001

xfzhu@ihcams.ac.cn

Xiaofan Zhu, MD principal investigator

Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC

27 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in China, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jingliao Zhang, MD (+86 22 23909196, zhangjingliao@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06764238, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.