NCT06220487

A Single-arm, Open-label Study of Olverembatinib, CD3/CD19 Bispecific T-cell Engager, and Chidamide in Patients With Newly Diagnosed Ph+ALL

A Single-arm, Open-label Study of Olverembatinib, CD3/CD19 Bispecific T-cell Engager, and Chidamide in Patients With Newly Diagnosed Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 67 (estimated)
• Sponsor: Nanfang Hospital, Southern Medical University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

ABC study is a phase 2, single-arm, open-label study of Olverembatinib, CD3/CD19 Bispecific T-cell Engager, and Chidamide in patients with newly diagnosed Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ALL). This study combined third generation TKI (Olverembatinib), histone deacetylase inhibitors (Chidamide) and CD3/CD19 bispecific T-cell engager (Blinatumomab) as first line regimen (ABC regimen) for Ph+ ALL. Investigatorsaim to explore the efficacy and safety of ABC regimen. The primary endpoint is the complete molecular remission （CMR） at 3 months, secondary endpoints are overall survival (OS), event-free survival (EFS), adverse event (AE), IKZF1del, IKZF1plus, IKZF1lpus/CD20 subgroup EFS/OS.

Detailed description

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is now a relatively favorable-risk leukemia with the development of potent BCR::ABL1 tyrosine kinase inhibitors (TKIs). Achievement of an early and deep complete molecular remission (CMR) is an important end point in Ph+ ALL and identifies patients who may not need allogeneic hematopoietic stem cell transplantation (allo-HSCT). The chemotherapy-free D-ALBA trial of dasatinib and blinatumomab was safe and effective in patients with newly diagnosed Ph-positive ALL and resulted in an estimated 3-year OS rate of 80% (NEJM 2020, 2022). To further improve the outcomes, the potent third-generation TKIs, ponatinib and olverembatinib (ASH 2023, abs 1504), were added to chemotherapy or immunotherapy, resulted in an overall CMR rate of 84%-90%, a 5-year survival rate of 73%, most patients did not undergo allo-HSCT. Of note, IKZF1plus subgroup still stands for high-risk for Ph+ALL and exhibit poor outcome even in TKI plus blinatumomab, which indicate IKZF1del confers resistance to immunotherapy. our previous study found that HDACi tucidinostat/chidamide could restore the expression and functionality of IKZF1 in IKZF1del samples, including increased expression of CD19 and reduced focal adhesion (Blood (2021) 138 (Supplement 1): 514.). ABC study is a phase 2, single-arm, open-label study of Olverembatinib, CD3/CD19 Bispecific T-cell Engager, and Chidamide in patients with newly diagnosed Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ALL). This study combined third generation TKI (Olverembatinib), histone deacetylase inhibitors (Chidamide) and CD3/CD19 bispecific T-cell engager (Blinatumomab) as first line regimen (ABC regimen) for Ph+ ALL. Investigators aim to explore the efficacy and safety of ABC regimen. The primary endpoint is the complete molecular remission （CMR） at 3 months, secondary endpoints are overall survival (OS), event-free survival (EFS), adverse event (AE), IKZF1del, IKZF1plus, IKZF1lpus/CD20 subgroup EFS/OS.

Conditions

• Acute Lymphoblastic Leukemia
• Philadelphia Chromosome
• Philadelphia-Positive ALL
• Adult ALL
• IKZF1 Gene Mutation

Interventions

Type	Name	Description
DRUG	Prednisone, Olverembatinib, Blinatumomab, Chidamide	Phase One. Induction Consolidation, for 1 year. 1.1 Pretreatment ×1 cycle. Prednisone，1mg/kg/d, from day 1 to 14; 1.2 Induction Therapy × 1 cycle. A: OlverembAtinib (at a dose of 40 mg Qod), from day 8 to 42. B: Blinatumomab (at a dose of 28 μg per day), from day 15 to 28. C: Chidamide (at a dose of 10 mg Qod), from day 9 to 41. 1.3 Consolidation Block × 5 cycles. A: Olverembatinib (at a dose of 40 mg Qod) was administered from day 1 to 42. B: Blinatumomab (at a dose of 28 μg perday) was administered from day 1 to 14. C: Chidamide (at a dose of 10 mg Qod) was administered from day 14 to 41. Phase Two. Maintenance Therapy, for 3 years. 2.1 A: Olverembatinib (at a dose of 40 mg Qod) was administered from day 1 to 42. C: Chidamide (at a dose of 10 mg Qod) was administered from day 14 to 41. Phase Three. Follow-up, for 5 years.

Timeline

• Start date: 2024-02-01
• Primary completion: 2025-12-31
• Completion: 2028-01-01
• First posted: 2024-01-24
• Last updated: 2024-01-24

Locations

1 site across 1 country: China

Regulatory

• FDA-regulated drug study