NCT06424340

MB-dNPM1-TCR.1 in Relapsed/Refractory AML

A Phase I/II Trial of MB-dNPM1-TCR.1 in HLA-A*02:01-positive Patients With Relapsed or Refractory NPM1-mutated AML to Determine Safety and Obtain First Data on Efficacy

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Sponsor: Miltenyi Biomedicine GmbH · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this Phase I/II, single arm, prospective, open label, dose escalation trial is to assess safety, feasibility and efficacy of ex vivo expanded autologous T cells genetically modified to express a T cell receptor (TCR) specific for dNPM1 peptides restricted to human leukocyte antigen (HLA) A\*02:01 in patients with relapsed or refractory AML.

Detailed description

The investigational medicinal product (IMP) MB-dNPM1-TCR.1 is designed to effectively target malignant myeloid cells in patients suffering from relapsed or refractory Acute Myeloid Leukemia (AML) with mutated Nucleophosmin. Autologous T cells will be genetically engineered using a lentiviral vector to express a T cell receptor (TCR) specific for certain dNPM1 peptides restricted to human leukocyte antigen (HLA) A\*02:01. The dNPM1-TCR transduced T cells target specifically the HLA/dNPM1 peptide complex on the cell surface of leukemic myeloid cells and eliminate these. During the treatment, the patients will undergo a leukapheresis, a lymphodepleting chemotherapy and an administration of the expanded dNPM1-TCR transduced T cells. Phase I: Since this is a first in human trial the primary goal in phase I is to establish the recommended dose of MB-dNPM1-TCR.1 for phase II. We assess the maximum tolerated dose (MTD) with toxicity defined as patients experiencing dose limiting toxicity (DLT) until day 28 after infusion of MB-dNPM1-TCR.1. Therefore a BOIN trial design will be used to guide dose escalation and de-escalation decisions in phase I. Phase II: The second phase will evaluate the efficacy and safety in patients treated with the recommended dose from phase I. The phase II part follows a Simon's 'minimax' two stage design.

Conditions

• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
BIOLOGICAL	MB-dNPM1-TCR.1	T Cell Receptor (TCR) T cell therapy

Timeline

• Start date: 2024-08-01
• Primary completion: 2028-06-01
• Completion: 2028-06-01
• First posted: 2024-05-22
• Last updated: 2026-04-16

Locations

1 site across 1 country: Netherlands