Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX] — AML-NET  

Acute Myeloid Leukemia Refractory Clinical Trial

Official title: A Phase I/II Study to Evaluate the Safety Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination With Standard AZACITIDINE+ VENETOCLAX in Patients With Refractory Acute Myeloid Leukemia

Status Recruiting

Clinical Trial Summary

The aim of this study is to investigate the safety and the clinical activities of NP137 when combined with Azacitidine and Venetoclax in patients with refractory acute myeloid leukemia after 2 cycles of Azacitidine and Venetoclax.

Clinical Trial Description

The dual treatment, VENETOCLAX and AZACITIDINE, is the standard of care for patients with newly diagnosed AML who are ineligible for intensive chemotherapy. However, upfront resistance as well as relapse following initial response demonstrate the need to improve this therapeutic strategy. NP137 is a first-in-class humanized monoclonal antibody targeting specifically and selectively Netrin-1. Based on data collected from non clinical studies NP137 should act in synergy with VENETOCLAX and AZACITIDINE to reactivate and enhance the apoptotic pathway in AML cells. The herein proposed study to assess the safety (Safety run in/ phase I part) and the preliminary efficacy signal (extension phase II part) of the NP137 when combined to AZACITIDINE AND VENETOCLAX in patients with refractory acute myeloid leukemia after 2 cycles of Azacitidine and Venetoclax. This study will be an open-label, Phase I/II trial. the first part, consists to a safety run to assess the security and the tolerability of the drugs combination from the first 6 to 12 first patients enrolled into the study. All patients will receive a fixed dose of NP137 at the RP2D (Recommended Phase 2 Dose) determined from the First in human NP137 study(DL1) . A dose deescalation of NP137 is planned to DL-1 according to the Dose Limiting Toxicities observed during this period. The second part will be will be then conducted as a phase II using an adaptive Bayesian approach allowing to quickly stop treatment without evidence of efficacy. The clinical activity will be assessed based on ELN (European LeukemiaNet) criteria 2027 for the Acute Myeloid Leukemia. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Refractory
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

• NCT number: NCT06150040
• Study type: Interventional
• Source: Centre Leon Berard
• Contact: Anne-Sophie MICHALET, MD
• Phone: 4 78 78 26 41
• Email: anne-sophie.michallet@lyon.unicancer.fr
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 4, 2023
• Completion date: November 30, 2027