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

Acute Lymphoblastic Leukemia Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Adult ALL
• Leukemia
• Leukemia, Lymphoid
• Philadelphia Chromosome
• Philadelphia-Positive ALL
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

• NCT number: NCT06220487
• Study type: Interventional
• Source: Nanfang Hospital, Southern Medical University
• Contact: Hongsheng Zhou, M.D; Ph.D
• Phone: +862062787349
• Email: hanson_tcm@hotmail.com
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2024
• Completion date: January 1, 2028