Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06764238

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Acute Lymphoblastic Leukemia ALL B Cell Acute Lymphoblastic Leukemia (B-ALL) Burkitt Lymphoma Childhood Leukemia, Acute Lymphoblastic DNA Virus Infections Epstein-Barr Virus Infections Hematologic Diseases Hemic and Lymphatic Diseases Herpesviridae Infections Immune System Diseases Immunoproliferative Disorders Infections Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma Tumor Virus Infections Virus Diseases

Age range

1 month–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Anhui Medical University Second Affiliated Hospital, Hefei, Anhui, China

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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)

Treatment and study plan

Blinatumomab (Group A)

Drug

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

Venetoclax (nonRand Group)

Drug

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, vincristine, dexamethasone

Blinatumomab (Group B)

Drug

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

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

    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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

Other outcomes

  1. 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.

  2. 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.

  3. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Jingliao Zhang, MD

CONTACT

[email protected]

+86 22 23909196

Xiaofan Zhu, MD

CONTACT

[email protected]

+ 86 22 23909001

Sponsors and collaborators

Lead sponsor

Institute of Hematology & Blood Diseases Hospital, China

Other

Registry information

Official study title

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

Acronym: CCCG-I/HR-ALL

Important dates

Study start
2025
Primary completion
2029
Study completion
2031
First posted
Jan 8, 2025
Registry last updated
Jul 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.