Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Nov 10;23(1):1090.
doi: 10.1186/s12885-023-11610-x.

Phase I non-randomized clinical trial of allogeneic natural killer cells infusion in acute myeloid leukemia patients

Mohammad Ahmadvand #  1 , Mahdieh Shokrollahi Barough #  2 , Maryam Barkhordar  3 , Ali Faridfar  2 , Afshin Ghaderi  4 , Hasan Jalaeikhoo  5 , Mohsen Rajaienejad  2 , Keivan Majidzadeh  6 , Ardeshir Ghavamzadeh  7   8 , Ramin Sarrami-Forooshani  9
Affiliations
Clinical Trial

Phase I non-randomized clinical trial of allogeneic natural killer cells infusion in acute myeloid leukemia patients

Mohammad Ahmadvand et al. BMC Cancer. .

Abstract

Introduction: A new type of immune cell transplantation called allogeneic NK cell infusion is proposed as a potential universal off-the-shelf cell product for adoptive immune cell therapy in hematologic malignancies.

Design: A multicentral phase I non-randomized clinical trial was conducted to assess the safety, feasibility, and potential efficacy of adoptively infused NK cells in patients with refractory/relapsed AML. We evaluated the feasibility of the trial by considering cell production, patient selection, and treatment protocol.

Method: Allogeneic NK cells were produced from random healthy unrelated donors; 10 patients were selected according to the inclusion criteria and were included in two groups in case of NK cell dose escalation. Two cell infusions were given, spaced 7 days apart, following a lymphodepletion conditioning regimen of fludarabin-endoxan administered 7 days before the first infusion. The intervention safety was scored using Common Terminology Criteria for Adverse Events (CTCAE) based on variations in vital signs due to cell infusion. NK cell chimerism, tumor burden, and duration of relapse were considered to be components of efficacy. The pilot feasibility evaluation was checked using the CONSORT platform.

Results: The NK cell infusion procedure was well tolerated, and no grade 2-5 toxicities related (possible or probable) to PB-NK cell infusion were observed. Four patients developed grade 1 transient chills, headaches, vomiting, and bone pain following each PB-NK cell infusion that were not required hospitalization. One of these patients (p01) died because of severe acute respiratory syndrome. Of 9 evaluable patients, 6 (66.6%) showed stable disease (SD) and 3 (33.3%) presented progressive disease (PD). Of 6 SD patients, 2 (p08 and p09) remained alive in SD and 3 patients (p04, p05 and p07) converted to PD at 9 months after infusion of NK cells, and 1 (p03) was not evaluable due to follow-up loss. No patient achieved complete remission.

Conclusion: The study demonstrated the feasibility and safety of adoptive transfer of random healthy unrelated donor PB-NK cells in refractory/relapsed AML patients and supports continued study in phase II clinical trials in relapsed/refractory AML patients.

Keywords: Acute Myeloid Leukemia (AML); Adoptive transfer; Allogeneic NK cell therapy; Cellular therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Expanded PB-NK cells reveal an active phenotype before infusion. A, Characterization of CD56+ cells in case of IFN-γ and CD107a expression against K562 targets (E:T ratio = 1:1). B, NK: K562 co-culture with the final product of NK cell expansion
See this image and copyright information in PMC

References

    1. Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, et al. Diagnosis and management of acute Myeloid Leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood the Journal of the American Society of Hematology. 2010;115(3):453–74. - PubMed
    1. Juliusson G, Antunovic P, Derolf Ã, Lehmann S, Möllgård L, Stockelberg D, et al. Age and acute Myeloid Leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. J Am Soc Hematol. 2009;113(18):4179–87. - PubMed
    1. He P, Liang J, Zhang W, Lin S, Wu H, Li Q, et al. Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia: An Overview of Systematic Reviews. 2022;2022:1828223. - PMC - PubMed
    1. Barr R, Creutzig U, Kutny MA, Schlenk RF, Ribeiro RC. Acute myelogenous Leukemia in adolescents and young adults. Pediatr Blood Cancer. 2018;65(9):e27089. doi: 10.1002/pbc.27089. - DOI - PMC - PubMed
    1. Kiessling R, Klein E, Pross H, Wigzell H. „Natural“ killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney Leukemia cells. Characteristics of the killer cell. Eur J Immunol. 1975;5(2):117–21. doi: 10.1002/eji.1830050209. - DOI - PubMed

Publication types

MeSH terms

Substances