Newly-diagnosed Intermediate/High Risk Pediatric B-cell ALL Protocol (CCCG-I/HR-ALL)

February 4, 2025 updated by: Institute of Hematology & Blood Diseases Hospital, China

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:

  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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

1800

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Chongqing, China
        • Not yet recruiting
        • Chongqing Medical University Affiliated Children's Hospital
        • Contact:
      • Shanghai, China
        • Not yet recruiting
        • Children's Hospital of Fudan University
        • Contact:
      • Shanghai, China
        • Not yet recruiting
        • Shanghai Children's Hospital
        • Contact:
      • Shanghai, China
        • Not yet recruiting
        • Shanghai Children's Medical Cener, Shanghai Jiao Tong University School of Medicine
        • Contact:
      • Shenzhen, China
        • Not yet recruiting
        • Shenzhen Children's Hospital
        • Contact:
    • Anhui
      • Hefei, Anhui, China
        • Not yet recruiting
        • Anhui Provincial Children's Hospital
        • Contact:
      • Hefei, Anhui, China
        • Not yet recruiting
        • Anhui Medical University Second Affiliated Hospital
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China
        • Not yet recruiting
        • Fujian Medical University Union Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Not yet recruiting
        • Nanfang Hospital, Southern Medical University
        • Contact:
      • Guangzhou, Guangdong, China
        • Not yet recruiting
        • Guangzhou Women And Children's Medical Center
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China
        • Not yet recruiting
        • The People's Hospital of Guangxi Zhuang Autonomous Region
        • Contact:
    • Guizhou
      • Guiyang, Guizhou, China
        • Not yet recruiting
        • The Affiliated Hospital of Guizhou Medical University
        • Contact:
    • Hubei
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
        • Contact:
      • Wuhan, Hubei, China
        • Not yet recruiting
        • Wuhan Children's Hospital
        • Contact:
    • Hunan
      • Changsha, Hunan, China
        • Not yet recruiting
        • Xiangya Hospital Central South University
        • Contact:
      • Changsha, Hunan, China
        • Not yet recruiting
        • Hunan Children's Hospital
        • Contact:
    • Jiangsu
      • Nanjing, Jiangsu, China
        • Not yet recruiting
        • Nanjing Children's Hospital Affiliated to Nanjing Medical University
        • Contact:
          • Yongjun Fang, MD
          • Phone Number: 025-83117500
          • Email: fyj322@189.cn
      • Suzhou, Jiangsu, China
        • Not yet recruiting
        • Children's Hospital of Soochow University
        • Contact:
    • Jiangxi
      • Nanchang, Jiangxi, China
        • Not yet recruiting
        • Jiangxi Provincial Children's Hospital
        • Contact:
    • Shandong
      • Jinan, Shandong, China
        • Not yet recruiting
        • Qilu Hospital of Shandong University
        • Contact:
      • Qingdao, Shandong, China
        • Not yet recruiting
        • Affiliated Hospital of Qingdao University
        • Contact:
    • Shanxi
      • Xi'an, Shanxi, China
        • Not yet recruiting
        • Xi'an Northwest Women and Children Hospital
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China
        • Not yet recruiting
        • West China Second University Hospital, Sichuan University
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Recruiting
        • Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC
        • Contact:
        • Contact:
          • Xiaofan Zhu, MD
        • Contact:
          • Jingliao Zhang, MD
  • Hong Kong
      • Hong Kong, Hong Kong
        • Not yet recruiting
        • Hong Kong Children's Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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)
Drug: Blinatumomab (Group A)
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
Other Names:
  • high-dose methotrexate
Experimental: 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).
Drug: Blinatumomab (Group B)
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
Other Names:
  • high-dose methotrexate
Experimental: 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.
Drug: Venetoclax (nonRand Group)
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
Other Names:
  • cyclophosphamide
  • dexamethasone
  • vincristine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
Up to 30 days after last dose of study treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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].
Time Frame: Up to five years
Proportions of patients with positive IgH NGS MRD in each arm will be estimated by the sample proportion along with the 95% confidence interval. The NGS MRD positive proportions will be compared by the two-sample z test. If the NGS MRD positive proportions are very low in one or both arms, Fisher's exact test will be applied.
Up to five years
Cellular immune-status prior to Blinatumomab-HDMTX consolidation therapy
Time Frame: At the end of induction
Descriptive statistics on T lymphocytes functions (exhaustion, activation, TCR diversity, etc.) including correlation coefficients (Pearson's or Spearman's) and regression modeling including possibly longitudinal data models will be applied as appropriate to analyze the biological associations.
At the end of induction
Cellular immune functions after blinatumomab-HDMTX consolidation
Time Frame: Up to 2 years
Descriptive statistics on T lymphocytes functions (exhaustion, activation, TCR diversity, etc.).including correlation coefficients (Pearson's or Spearman's) and regression modeling including possibly longitudinal data models will be applied as appropriate to analyze the biological associations.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Investigators

  • Principal Investigator: Xiaofan Zhu, MD, Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 3, 2025

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

June 1, 2031

Study Registration Dates

First Submitted

December 20, 2024

First Submitted That Met QC Criteria

January 1, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 4, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT2024068

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

  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.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: CCCG-ALL
    Information comments: CCCG-ALL-2025 DATASET

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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