Newly-diagnosed Low Risk Pediatric B-cell ALL Protocol

Last updated: March 11, 2025
Sponsor: Institute of Hematology & Blood Diseases Hospital, China
Overall Status: Active - Not Recruiting

Phase

2/3

Condition

Leukemia

Treatment

Chemo-light Maintenance 2

Blinatumomab

Reinduction-2 omission

Clinical Study ID

NCT06882057
IIT2025021
  • Ages 1-18
  • All Genders

Study 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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

Must meet all items below:

  1. Age older than 1 year and younger than 18 years.

  2. Diagnosis of acute lymphoblastic leukemia by bone marrow morphology.

  3. Diagnosis of B-ALL by immunophenotyping.

  4. Low risk group

Exclusion

Exclusion Criteria:

Should be excluded in the presence of any item below:

  1. T-ALL

  2. I/HR B-ALL group

  3. sIgM+

  4. Acute leukemias of ambiguous lineage diagnosed according to WHO or EGIL criteria.

  5. Philadelphia chromosome positive ALL (Ph-ALL)

  6. ALL evolved from chronic myeloid leukemia (CML).

  7. Down's syndrome, or major congenital or hereditary disease with organ dysfunction

  8. Secondary leukemia

  9. Known underlying congenital immunodeficiency or metabolic disease

  10. Congenital heart disease with cardiac insufficiency.

  11. Glucocorticoid treatment for ≥14 days, or ABL kinase inhibitors for > 7 days withinone month before enrollment, or any chemotherapy or radiotherapy within 3 monthsbefore enrollment (except for emergency radiotherapy to relieve airway compression)

Study Design

Total Participants: 3000
Treatment Group(s): 3
Primary Treatment: Chemo-light Maintenance 2
Phase: 2/3
Study Start date:
March 01, 2025
Estimated Completion Date:
June 30, 2033

Study Description

  1. 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).

  2. Two courses of HD-MTX will be administered as consolidation phase, maintaining the same dose of 3 g/m².

  3. Second 14 days of blinatumomab will be given after completion of HDMTX consolidation treatment .

  4. Adding IgH rearrangement NGS MRD as an evaluation indicator. Reinduction-2 will be omitted for patients with NGS-MRD46<10-6 who have receive the second course of Blina-14. (Reinduction-2 should be given regardless of NGS-MRD 46 status in patients who did not receive the second course of binatumomab).

  5. A total of four repeating courses will be applied in Maintenance 1 (in contrast to 5 courses in 2020 protocol). Additionally, one-week rest period will be implemented after each course to ensure safety and optimal efficacy.

  6. 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). The other patients with higher levels of MRD by FCM MRD or NGS MRD will receive maintenance-2 with 9 cycles of 8-week course of MTX + 6MP for a total of 72 weeks (same as CCCG-ALL2020)

  7. Bone Marrow Aspiration Assessment (BMA): One additional bone marrow puncture at the end of 1st Blina-14 course (Day60 MRD) will be performed at early intensification phase. This results in a total of 4 BMAs in the CCCG2025-LR protocol, in contrast to 3 BMAs in 2020 protocol.

  8. Triple Intrathecal Therapy (TIT):In the HDMTX consolidation phase, there will be two TITs in contrast to four treatments in the CCCG2020 protocol. To compensate for this reduction, two additional TIT treatments will be administrated before the 1st and 2nd Blina-14 courses. Additionally, two intrathecal treatments will be added during Reinduction 1 and Reinduction 2 to further enhance CNS control. Meanwhile, one TIT will be reduced in the Maintenance-1 phase compared to 2020 protocol. This results in a total of 16 or 17 TITs, depending on whether the second Blina-14 course is applied This is similar to the CCCG2020, where 16 or 17 TITs are administrated depending on whether CAT+ was given).

  9. Adding pharmacotyping study for LR B-ALL.

  10. Treatment duration: The treatment duration for the CCCG-LR-ALL-2020 protocol is 121/124 weeks (depending on if CAT+ was given). In the CCCG-LR-ALL-2025 protocol:

    • For patients with NGS MRD46 ≥10-6, the total treatment duration is 123 weeks. Key changes include: 2 weeks of Blina-14 replacing 3 weeks of CAT+, 2 courses of HDMTX reduction (4 weeks), and an additional 2 weeks for the 2nd blina-14 course added following HDMTX;

    • For patients with MRD19≥ 0.01% and NGS MRD46 < 10-6 who subsequently receive 2nd Blina-14, Reinduction-2 is omitted, shortening the total duration by 3 weeks. (120 weeks in total). If the 2nd Blina-14 is not administrated, Reinduction -2 will still be included, resulting in a total duration of 121 weeks.

    • For patients with MRD19 < 0.01% and NGS MRD46 < 10-6, who subsequently receive 2nd Blina-14, both the Reinduction-2 (3 weeks) and the subsequent 5 cycles of Maintenance-2 (40 weeks) are omitted. This results in a total treatment duration of 80 weeks (81 weeks if 2nd Blina-14 is not applied).

Connect with a study center

  • Anhui Medical University Second Affiliated Hospital

    Hefei, Anhui
    China

    Site Not Available

  • Anhui Provincial Children's Hospital

    Hefei,, Anhui
    China

    Site Not Available

  • Chongqing Medical University Affiliated Children's Hospital

    Chongqing, Chongqing
    China

    Site Not Available

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian
    China

    Site Not Available

  • Guangzhou Women and Children's Medical Center

    Guangzhou, Guangdong
    China

    Site Not Available

  • Nanfang Hospital, Southern Medical University

    Guangzhou, Guangdong
    China

    Site Not Available

  • The People's Hospital of Guangxi Zhuang Autonomous Region

    Nanning, Guangxi
    China

    Site Not Available

  • The Affiliated Hospital of Guizhou Medical University

    Guiyang, Guizhou
    China

    Site Not Available

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

    Wuhan, Hubei
    China

    Site Not Available

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

    Wuhan, Hubei
    China

    Site Not Available

  • Wuhan Children's Hospital

    Wuhan, Hubei
    China

    Site Not Available

  • Hunan Children's Hospital

    Changsha, Hunan
    China

    Site Not Available

  • Xiangya Hospital Central South University

    Changsha, Hunan
    China

    Site Not Available

  • Nanjing Children's Hospital Affiliated to Nanjing Medical University

    Nanjing, Jiangsu
    China

    Site Not Available

  • Children's Hospital of Soochow University

    Soochow, Jiangsu
    China

    Site Not Available

  • Jiangxi Provincial Children's Hospital

    Nanchang, Jiangxi
    China

    Site Not Available

  • Qilu Hospital of Shandong University

    Jinan, Shandong
    China

    Site Not Available

  • Affiliated Hospital of Qingdao University

    Qingdao, Shandong
    China

    Site Not Available

  • Children's Hospital of Fudan University

    Shanghai, Shanghai
    China

    Site Not Available

  • Shanghai Children's Hospital

    Shanghai, Shanghai
    China

    Site Not Available

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

    Shanghai, Shanghai
    China

    Site Not Available

  • Xi'an Northwest Women and Children Hospital

    Xi'an, Shanxi
    China

    Site Not Available

  • Shenzhen Children's Hospita

    Shenzhen, Shenzhen
    China

    Site Not Available

  • West China Second University Hospital

    Chengdu, Sichuan
    China

    Site Not Available

  • Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC

    Tianjin, Tianjin
    China

    Site Not Available

  • Hong Kong Children's Hospital

    Hong Kong,
    Hong Kong

    Site Not Available

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