Newly-diagnosed Low Risk Pediatric B-cell ALL Protocol (CCCG-LR-B-ALL)

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Enrolling; Phase 3; Phase 2

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

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

Study type: Interventional

Funder types: Other

Identifiers

NCT06882057

IIT2025021

Details and patient eligibility

About

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).

Full 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).

Enrollment: 3,000 estimated patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

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 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 within one month before enrollment, or any chemotherapy or radiotherapy within 3 months before enrollment (except for emergency radiotherapy to relieve airway compression)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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3,000 participants in 3 patient groups

NGS MRD46 ≥ 10^-6

Experimental group

Description:

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

Treatment:

Drug: Blinatumomab

MRD19≥ 0.01% and NGS MRD46 < 10^-6

Experimental group

Description:

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 group

Description:

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

Treatment:

Drug: Chemo-light Maintenance 2

Drug: Blinatumomab

Drug: Reinduction-2 omission