NCT02809092

A Phase I/II Clinical Trial Testing the Safety and Feasibility of IL-21- Expanded Natural Killer Cells for the Induction of Relapsed/Refractory Acute Myeloid Leukemia

Status unknown Phase 1/Phase 2 Last updated 11 October 2019

What this trial tests

Phase 1/Phase 2 trial testing NK Cells + Chemotherapy Starting in Acute Myeloid Leukemia in 30 participants. Status unknown.

Timeline

1 April 2017

Primary endpoint
30 September 2019

1 September 2020

Quick facts

Lead sponsor	Hospital de Clinicas de Porto Alegre
Phase	Phase 1/Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	1 April 2017
Primary completion	30 September 2019
Estimated completion	1 September 2020
Sites	1 location across Brazil

Drugs / interventions tested

• NK Cells + Chemotherapy Starting — full drug profile →

Conditions studied

• Acute Myeloid Leukemia — all drugs for Acute Myeloid Leukemia →

Sponsor

Hospital de Clinicas de Porto Alegre

Who can join

Adults 2 to 59, any sex, with Acute Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Maximum Tolerated Dose (MTD) of membrane-bound interleukin 21 (mbIL21)-Expanded Haploidentical NK Cells After Induction Chemotherapy with Fludarabine, Cytarabine, and Granulocyte-colony stimulating factor (G-CSF).
  Time frame: 28 days
  Maximum tolerated dose defined as highest dose studied in which 6 patients have been treated and at most 2 patients with dose-limiting toxicities (DLTs) observed. A dose-limiting toxicity (DLT) is defined as: Acute severe (grade 3 or 4) infusional allergic reaction related to the NK cells infusion. Prolonged cytopenia beyond D+28. If neutropenia is still present at day 28, that will trigger the

Sponsor's own description

Relapsed acute myeloblastic leukemia (AML) requires remission prior to allogeneic Hematopoietic Stem Cell Transplant (HSCT) for optimal survival, but is a disease with poor response to chemotherapy. Human leukocyte antigen (HLA) haploidentical, Natural killer (NK) enriched peripheral blood cell infusions have shown safety in patients with poor prognosis AML. Though not powered for such an assessment, this trial showed a promising but not statistically significant trend in remission rate. NK cell therapy was limited by small numbers of NK cells attainable through leukapheresis. We have now demonstrated that large numbers of NK cells can be propagated ex vivo from a small volume blood draw, obviating the need for donor leukapheresis. The purpose of this trial is to determine the feasibility and maximum tolerated dose of expanded NK cells and estimate the toxicity of treating relapsed/refractory AML with fludarabine + high-dose cytarabine + G-CSF (FLAG) chemotherapy followed by haploidentical expanded natural killer (NK) cells.

The first NK cell dosing cohort will be well below the currently-established safe dose of pheresis-derived NK cells, as expanded NK cells may have increased toxicity because of their activated phenotype. In order to avoid accruing patients at suboptimal doses, a dose escalation schema based on the principles of an accelerated titration design is used in this study to allow expeditious advancement up to the current safe dose of NK cells.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer Immunotherapy.
   Lupo KB, Matosevic S. · · 2019 · cited 146× · PMID 31163679 · DOI 10.3390/cancers11060769
2. Natural killer cells: a promising immunotherapy for cancer.
   Chu J, Gao F, Yan M, Zhao S, et al · · 2022 · cited 140× · PMID 35606854 · DOI 10.1186/s12967-022-03437-0
3. NK Cell-Based Immunotherapies in Cancer.
   Shin MH, Kim J, Lim SA, Kim J, et al · · 2020 · cited 103× · PMID 32395366 · DOI 10.4110/in.2020.20.e14
4. Cell therapies in the clinic.
   Wang LL, Janes ME, Kumbhojkar N, Kapate N, et al · · 2021 · cited 99× · PMID 34027097 · DOI 10.1002/btm2.10214
5. Natural killer cell-based immunotherapy for acute myeloid leukemia.
   Xu J, Niu T. · · 2020 · cited 83× · PMID 33287858 · DOI 10.1186/s13045-020-00996-x
6. Inflammation in cancer: therapeutic opportunities from new insights.
   Xie Y, Liu F, Wu Y, Zhu Y, et al · · 2025 · cited 53× · PMID 39994787 · DOI 10.1186/s12943-025-02243-8
7. Understanding NK cell biology for harnessing NK cell therapies: targeting cancer and beyond.
   Shin E, Bak SH, Park T, Kim JW, et al · · 2023 · cited 46× · PMID 37539051 · DOI 10.3389/fimmu.2023.1192907
8. Enhancing a Natural Killer: Modification of NK Cells for Cancer Immunotherapy.
   Islam R, Pupovac A, Evtimov V, Boyd N, et al · · 2021 · cited 27× · PMID 33946954 · DOI 10.3390/cells10051058