NCT03348033

Safety and Feasibility of the Use of Natural Killer Cells in Patients With Chronic Myeloid Leukemia

Adoptive Immunotherapy in Patients With Chronic Myeloid Leukemia: Phase I/II Study to Test the Safety and Feasibility of Autologous Activated and Expanded Natural Killer Cells

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 5 (estimated)
• Sponsor: Hospital de Clinicas de Porto Alegre · Academic / Other
• Sex: All
• Age: 2 Years – 59 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate safety, feasibility and maximum tolerated dose of NK cells cultured in vitro as adjuvant treatment of patients with chronic myeloid leukemia candidates to allogenic bone marrow transplantation or refractory to conventional treatment.

Detailed description

Natural killer (NK) cells are one of the main type of immune cells that mediate the graft-versus-leukemia (GVL) effect. They are a fundamental part of innate immunity, with a major role in rapid response against infectious agents and activating immune system against tumoral cells. Patients with chronic myelogenous leukemia (CML), however, seem to have lower NK cell counts as disease progresses from chronic phase to blast crisis, as well as diminished cytotoxicity in those NK cells remaining. Therapeutic role of the NK cell ability to target certain specific cells is currently being studied, especially regarding their action against tumoral cells. Chronic myeloid leukemia studies with NK cells have so far demonstrated that autologous ex vivo activated NK cells are able to suppress in vitro the presence of the breakpoint cluster region-abelson leukemia virus (BCR-ABL) oncogene. These studies have demonstrated that adoptive NK cell therapy may have a potential role in treatment of CML patients. The purpose of this study is to evaluate safety, feasibility and maximum tolerated dose of NK cells cultured in vitro as adjuvant treatment of patients with chronic myeloid leukemia candidates to allogenic bone marrow transplantation or refractory to conventional treatment. NK cells will be expanded from peripheral blood mononuclear cells after depletion of T cells. They ar going to be co-cultured with clone 9 K562 artificial antigen presenting cell (aAPCs), which are posteriorly modified to also express membrane interleukin-21 (mIL-21)

Conditions

• Chronic Myeloid Leukemia

Interventions

Type	Name	Description
BIOLOGICAL	Chronic Myeloid Leukemia + NK cell	Patients with chronic phase chronic myeloid leukemia who lost response to the second line of treatment with tyrosine kinase inhibitor with indication of bone marrow transplantation or refractory. Infusion of autologous natural killer cells, expanded in the laboratory, after chemotherapeutic conditioning.

Timeline

• Start date: 2019-03-01
• Primary completion: 2021-03-01
• Completion: 2023-03-01
• First posted: 2017-11-20
• Last updated: 2019-03-12

Locations

1 site across 1 country: Brazil