An Open-label, Phase I Study to Assess the Safety of NKR-2 Treatment Administered Concurrently With 5-azacytidine in Treatment-naïve Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients Not Candidates for Intensive Therapy

Brief Summary

Detailed Description

This open-label Phase I study aims to define the recommended dose for further clinical development the NKR-2 treatment administered concurrently with AZA in treatment-naïve AML/MDS patients not candidates for intensive induction chemotherapy. The treatment consists in six consecutive cycles of AZA, administered at days 1. to 7 of a 28-day cycle. Patients will be treated with 8 injections of NKR-2 at day 9 and 23 of AZA cycles 2-3-4 and 5. This Phase I study is divided into three sequential cohorts evaluating three different dose-levels of NKR-2 (1x108, 3x108 and 1x109 NKR-2 per injection) using a 3+3 design. Further patients will be enrolled at the RecD to reach 9 evaluable patients in total at the RecD. The study consists of a screening phase, a treatment administration phase and a follow-up phase divided into treatment follow-up (TFU) and long-term safety follow-up (LTSFU). For each patient who received at least one NKR- 2. administration, the overall study duration will be 15 years after first NKR- 2 administration. Patients will be asked to complete a total of 54 visits during the treatment administration phase, and 5 visits during the treatment follow-up phase. During the LTSFU, yearly visits will be scheduled (up to Visit Y15).

Primary Outcomes

Secondary Outcomes

• Additional Safety Endpoint: the occurrence of Adverse Events and Serious Adverse Events and any toxicity linked to study participation until the end of the administration phase, and until the end of the treatment follow-up.(Study enrollment until the 24 month study visit.)
• Overall Survival (OS) Follow-Up(Study enrollment until the 24 month study visit.)
• Non-relapse Mortality Rate (NMR)(Study enrollment until the 24 month study visit.)
• First Objective Clinical Response(Study enrollment until the 24 month study visit.)
• Duration of First Objective Clinical Response(Study enrollment until the 24 month study visit.)
• Second Overall Clinical Response(Study enrollment until the 24 month study visit.)
• Relapse-Free Survival (RFS) Follow-Up(Study enrollment until the 24 month study visit.)
• Event Free Survival (EFS) Follow-Up(Study enrollment until the 24 month study visit.)
• Duration of Second Overall Clinical Response(Study enrollment until the 24 month study visit.)
• Cumulative Incidence of Relapse(Study enrollment until the 24 month study visit.)
• Cumulative Incidence of Death(Study enrollment until the 24 month study visit.)
• AML Incidence of Response(Study enrollment until the 24 month study visit.)
• MDS Incidence of Response(Study enrollment until the 24 month study visit.)
• Allogeneic Bone Marrow Transplant(Study enrollment until the 24 month study visit.)