NCT07152041

Newly-diagnosed Pediatric Ph-positive B-ALL Protocol

A Phase 3, Multicenter Trial for Pediatric Philadelphia Chromosome-positive B-Acute Lymphoblastic Leukemia -2025 Project

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 1 Month – 18 Years
• Healthy volunteers: Not accepted

Summary

This prospective clinical trial evaluates the effectiveness and safety of "chemotherapy-light" regimen incorporating the third-generation TKI olverembatinib, the bi-specific CD3/CD19 T cell engager blinatumomab, and the BCL-2 selective inhibitor venetoclax for newly diagnosed pediatric/adolescent patients with Ph+ ALL. The CCCG-Ph+ B-ALL-2025 protocol will be modified as following compared to the CCCG-ALL-2020 protocol

Detailed description

1. All Ph+-ALL patients will uniformly use the 3rd generation of TKI olverembatinib (OVB) instead of dasatinib throughout the regimen. 2. OVB is combined with Vincristine and Prednisone (VP) during the first 2 weeks and with blinatumomab during the last 4 weeks of remission induction in this protocol. 3. Patients will receive blinatumomab for 28 days as induction instead of CAT to improve induction response and avoid toxicity. 4. All patients will receive two cycles of HDMTX+Blina-14 and 4 times of triple intrathecal therapy (TIT) throughout the consolidation 1 phase. 5. To decrease the toxicities of high-dose AraC, the dosage will be reduced to 1 g/m2 in the consolidation 2 phase in contrast to 2 g/m2 in 2020 protocol. 6. Throughout the early Maintenance Therapy, dexamethasone and vincristine combination will be added with either venetoclax or daunorubicin alternatively for five cycles, given after MTX and 6-MP. 7. Cyclophosphamide and asparaginase are totally omitted from the entire treatment to mitigate toxicities. 8. Olverembatinib concentrations are recommended to be examined (cerebrospinal fluid and peripheral blood in parallel) before OVB given, after full dosing of OVB, and/or Blina+OVB, best to match lumbar puncture assessments timepoints. 9. IgH rearrangement by NGS MRD will be added as an evaluation indicator, with testing frequency matching bone marrow aspiration assessments. 10. Pharmarcotyping studies are recommended at baseline if condition permits. 11. For patients who cannot use full-dose blinatumomab, we will adopt the CCCG-Ph+ALL2020 protocol. complications.

Conditions

• Acute Lymphoblastic Leukemia (ALL) Philadelphia Chromosome-positive (Ph+)
• Childhood Leukemia, Acute Lymphoblastic

Interventions

Type	Name	Description
DRUG	olverembatinib	All Ph+-ALL patients will uniformly use the 3rd generation of TKI olverembatinib (OVB) instead of dasatinib throughout the regimen. OVB is combined with Vincristine and Prednisone (VP) during the first 2 weeks and with blinatumomab during the last 4 weeks of remission induction in this protocol. Patients will receive blinatumomab for 28 days as induction instead of CAT to improve induction response and avoid toxicity. All patients will receive two cycles of HDMTX+Blina-14 and 4 times of triple intrathecal therapy (TIT) throughout the consolidation 1 phase. To decrease the toxicities of high-dose AraC, the dosage will be reduced to 1 g/m2 in the consolidation 2 phase in contrast to 2 g/m2 in 2020 protocol. Throughout the early Maintenance Therapy, dexamethasone and vincristine combination will be added with either venetoclax or daunorubicin alternatively for five cycles, given after MTX and 6-MP.

Timeline

• Start date: 2025-03-28
• Primary completion: 2029-12-01
• Completion: 2030-06-01
• First posted: 2025-09-03
• Last updated: 2025-09-03

Locations

24 sites across 2 countries: China, Hong Kong