NCT06150040

Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX]

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: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Acute Myeloid Leukemia Refractory

Interventions

Type	Name	Description
DRUG	NP137	IV infusion, 14mg/kg or 9mg/kg, every 2 weeks
DRUG	Azacitidine Injection	Subcutaneous injection, 75 mg/m², on cycle Days 1-7 (28-days cycle)
DRUG	Venetoclax	Orally, 70 mg, every day on Days 1-28

Timeline

• Start date: 2024-09-11
• Primary completion: 2025-02-18
• Completion: 2025-02-18
• First posted: 2023-11-29
• Last updated: 2025-02-20

Locations

1 site across 1 country: France