Newly-diagnosed Low Risk Pediatric B-cell ALL Protocol

NCT06882057 | Recruiting Phase 2 DMC

• 1 other identifier: IIT2025021
• Study Type: interventional
• Target: 3,000
• Locations: 2 countries
• Sites: 27

Brief Summary

CCCG-ALL2025 LR-B-ALL plan is designed based on the CCCG-ALL2020 plan. This is a clinical trial using 14 days of blinatumomab (Blina-14) as early intensification after induction therapy and 2nd Blina-14 in consolidation therapy in all newly diagnosed provisional low-risk (LR) pediatric acute lymphoblastic leukemia (ALL) patients, regardless of measurable residual diseases (MRD) status. We will compare the efficacy of chemotherapy combined with Blina-14, comparing to CAT+ intensification or historical regimens. Patients with early remission in depth will receive chemo-light late intensification and maintenance therapy afterwards. Early complete remission in depth and maintenance reduction will be determined by next-generation sequencing (Ig-NGS MRD).

Conditions

Acute Lymphoblastic Leukemia ALL; Childhood Leukemia, Acute Lymphoblastic; B Cell Acute Lymphoblastic Leukemia (B-ALL)

Keywords

blinatumomab; chemo-light

Outcome Measures

Primary Outcomes (1)

• Compare 3-year event-free survival (EFS) between patients who receive Blina-14 intensification with this historical controls from CCCG-ALL2015 and CCCG-ALL2000

  The primary historical control cohort consists of the patients on the CCCG-ALL2020 trial determined as LR after remission indiction, received 2xHDMTX during consolidation and did not receive Bliniatumomab. As of end of 2024, this cohort contains 1111 patients, with 3-year EFS 0.963 and standard error 0.0087, 95% confidence interval \[0.953,0.980\] . The sample size and power assessment below is based on these data. The primary comparison is between the patients on this trial who are determined as LR after remission induction to the historical cohort described above, on 3-year EFS probability. .Power of the above test procedure is assessed by a simulation study. Historical control is set from the preliminary data as S0=0.963,v0\^2=0.0087\^2. For the current trial total sample size is set to n=2325 with 5 year accrual.LN distribution is chosen for its good assemblance of the EFS functions of the LR cohorts in the historical data.

  The expected study duration is approximately 5 years.

Secondary Outcomes (9)

• Estimate event-free survival (EFS) in patients with deep remission (FCM MRD19<0.01% and Ig-NGS MRD46<10-6) who received Maintenance-2' with reduced intensity chemotherapy

  Approximately 6.5 years.

• Estimate overall survival (OS) in patients with deep remission (FCM MRD19<0.01% and Ig-NGS MRD46<10-6) who received Maintenance-2' with reduced intensity chemotherapy

  Approximately 6.5 years.

• Estimate cumulative incidence of relapse (CIR) in patients with deep remission (FCM MRD19<0.01% and Ig-NGS MRD46<10-6) who received Maintenance-2' with reduced intensity chemotherapy

  Approximately 6.5 years.

• Compare event-free survival (EFS) to those of historical cohorts (CCCG-ALL-2015 and CCCG-ALL2020)

  Approximately 6.5 years.

• Compare overall survival (OS) to those of historical cohorts (CCCG-ALL-2015 and CCCG-ALL2020)

  Approximately 6.5 years.

Other Outcomes (3)

• Compare the 3-year EFS between patients who received Blina-14 intensification with those who received CAT+ intensification

  Approximately 3.5 years

• Evaluate the significance of the early deep remission rate after Blina-14 intensification by its association with treatment outcomes, especially cumulative incidence of relapse (CIR)

  Approximately 6.5 years.

• Evaluate toxicities during the immuno-chemo combined therapy in provisional LR-ALL.

  Up to 30 days after last dose of study treatment

Study Arms (3)

NGS MRD46 ≥ 10^-6

EXPERIMENTAL

All LR-B-ALL patients will be treated with 14 days of blinatumomab (Blina-14) as early intensification to replace CAT+ (historically given in LR-B-AL with MRD19\>0.1% in the 2020 protocol). Additionally, second 14 days of blinatumomab will be given after completion of HDMTX consolidation treatment. Reinduction-2 and Maintenance-2 will be given in full doses

Drug: Blinatumomab

MRD19≥ 0.01% and NGS MRD46 < 10^-6

EXPERIMENTAL

All LR-B-ALL patients will be treated with 14 days of blinatumomab (Blina-14) as early intensification to replace CAT+ (historically given in LR-B-AL with MRD19\>0.1% in the 2020 protocol). Additionally, second 14 days of blinatumomab will be given after completion of HDMTX consolidation treatment. Reinduction-2 will be omitted, but Maintenance-2 will be given in full doses

MRD19 < 0.01% and NGS MRD46 < 10^-6

EXPERIMENTAL

All LR-B-ALL patients will be treated with 14 days of blinatumomab (Blina-14) as early intensification to replace CAT+ (historically given in LR-B-AL with MRD19\>0.1% in the 2020 protocol). Additionally, second 14 days of blinatumomab will be given after completion of HDMTX consolidation treatment. Reinduction-2 will be omitted, and 5 cycles of Maintenance-2 will be omitted

Drug: Blinatumomab; Drug: Reinduction-2 omission; Drug: Chemo-light Maintenance 2

Interventions

Blinatumomab DRUG

All LR-B-ALL patients will be treated with 14 days of blinatumomab (Blina-14) as early intensification to replace CAT+ (historically given in LR-B-AL with MRD19\>0.1% in the 2020 protocol). Additionally, second 14 days of blinatumomab will be given after completion of HDMTX consolidation treatment.

Also known as: Dexamethasone, Prednisone, Asparaginase, Vincristine, Cyclophosphomide, Cytarabine, 6-MP, Methotrexate, Daunorubicin

MRD19 < 0.01% and NGS MRD46 < 10^-6; NGS MRD46 ≥ 10^-6

Reinduction-2 omission DRUG

Reinduction-2 will be omitted for patients with NGS-MRD46\<10\^-6 who have receive the two courses of Blina-14.

Also known as: Dexamethasone, Prednisone, Daunorubicin, Asparaginase, Vincristine, Cyclophosphomide, Cytarabine, 6-MP, Methotrexate

MRD19 < 0.01% and NGS MRD46 < 10^-6

Chemo-light Maintenance 2 DRUG

Patients with FCM-MRD19\<0.01% and IgH rearrangement NGS MRD 46\<10\^-6 will receive chemo-light maintenance-2 with 4 cyles of 8-week course of MTX + 6MP (totally 32 weeks).

Also known as: Dexamethasone, Prednisone, Daunorubicin, Asparaginase, Vincristine, Cyclophosphomide, Cytarabine, 6-MP, Methotrexate

MRD19 < 0.01% and NGS MRD46 < 10^-6

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Must meet all items below:
• Age older than 1 year and younger than 18 years.
• Diagnosis of acute lymphoblastic leukemia by bone marrow morphology.
• Diagnosis of B-ALL by immunophenotyping.
• Low risk group

You may not qualify if:

• Should be excluded in the presence of any item below:
• T-ALL
• I/HR B-ALL group
• sIgM+
• Acute leukemias of ambiguous lineage diagnosed according to WHO or EGIL criteria.
• Philadelphia chromosome positive ALL (Ph-ALL)
• 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.
• Glucocorticoid treatment 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)

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (27)

Anhui Medical University Second Affiliated Hospital

Hefei, Anhui, China

NOT YET RECRUITING

Anhui Provincial Children's Hospital

Hefei, Anhui, China

NOT YET RECRUITING

Chongqing Medical University Affiliated Children's Hospital

Chongqing, Chongqing Municipality, China

NOT YET RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

NOT YET RECRUITING

Guangzhou Women and Children's Medical Center

Guangzhou, Guangdong, China

NOT YET RECRUITING

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

NOT YET RECRUITING

The People's Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, China

NOT YET RECRUITING

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, China

NOT YET RECRUITING

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

NOT YET RECRUITING

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

NOT YET RECRUITING

Wuhan Children's Hospital

Wuhan, Hubei, China

NOT YET RECRUITING

Hunan Children's Hospital

Changsha, Hunan, China

NOT YET RECRUITING

The Third Xiangya Hospital of the Central South University

Changsha, Hunan, China

NOT YET RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, China

NOT YET RECRUITING

Nanjing Children's Hospital Affiliated to Nanjing Medical University

Nanjing, Jiangsu, China

NOT YET RECRUITING

Children's Hospital of Soochow University

Suzhou, Jiangsu, China

NOT YET RECRUITING

Jiangxi Provincial Children's Hospital

Nanchang, Jiangxi, China

NOT YET RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, China

NOT YET RECRUITING

Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

NOT YET RECRUITING

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

Shanghai Children's Hospital

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

Shanghai Children's Medical Cener, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

Xi'an Northwest Women and Children Hospital

Xi’an, Shanxi, China

NOT YET RECRUITING

Shenzhen Children's Hospita

Shenzhen, Shenzhen, China

NOT YET RECRUITING

West China Second University Hospital

Chengdu, Sichuan, China

NOT YET RECRUITING

Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC

Tianjin, Tianjin Municipality, China

RECRUITING

Hong Kong Children's Hospital

Hong Kong, Hong Kong, Hong Kong

NOT YET RECRUITING

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Related Links

• CCCG-ALL-2025 DATASET

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma

Interventions

blinatumomab; Dexamethasone; Prednisone; Asparaginase; Vincristine; Cytarabine; Methotrexate; Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Pregnadienediols; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Xiaofan Zhu, MD

  Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaofan Zhu, MD

CONTACT

+ 86 22 23909001; xfzhu@ihcams.ac.cn

Jingliao Zhang, MD

CONTACT

+86 22 23909196; zhangjingliao@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 18, 2025
• Study Start: March 3, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): June 1, 2033
• Last Updated: August 26, 2025

Record last verified: 2025-08

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 2032, 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.

Locations

HK (1); CN (26)