Newly-diagnosed Intermediate/High Risk Pediatric B-cell ALL Protocol (CCCG-I/HR-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: Venetoclax (nonRand Group); Drug: Blinatumomab (Group A); Drug: Blinatumomab (Group B)

Study type: Interventional

Funder types: Other

Identifiers

NCT06764238

IIT2024068

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,800 estimated patients

Sex: All

Ages: 1 month to 18 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

1,800 participants in 3 patient groups

Group A

Experimental group

Description:

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)

Treatment:

Drug: Blinatumomab (Group A)

Group B

Experimental group

Description:

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).

Treatment:

Drug: Blinatumomab (Group B)

NonRandonmized Group

Experimental group

Description:

Patients who will not be subjected to blinatomomab randomization, will received PVDL + Venetoclax + mini-hyperCVD as induction phase , subsequently receiving CAT as early intensification.

Treatment:

Drug: Venetoclax (nonRand Group)