Acute myeloid leukemia
Conditions
Interventions
As preparative regimen to NK-cell administration patients receive chemotherapy
for 3 days, starting one week prior to a single intravenous administration of
NK-cells. Except 3 patients, the NK cell
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: MDS with excess blasts, MDS/AML or AML patients (de novo and secondary) according to ELN 2022 criteria, who have stable disease or non-rapidly progressive disease with or without disease controlling medication, who are not eligible for allogeneic SCT - Age > 18 years - WHO performance 0-2 - Life expectancy of > 4 months - Written informed consent - Hydrea is allowed as pre-treatment to control blast count until day -3 - Other disease controlling medication is allowed until day -7
Exclusion criteria
Exclusion criteria: - Progressive disease in case of previous therapy - Patients on immunosuppressive drugs or active GvHD - Patients with active infections (viral, bacterial or fungal); acute anti-infectious therapy must have been completed within 7 days prior to study treatment - Severe cardiovascular disease (CTCAE III-IV) - Severe pulmonary dysfunction (CTCAE III-IV) - Severe renal dysfunction (CTCAE III-IV) - Severe hepatic dysfunction (CTCAE III-IV) - Severe neurological or psychiatric dysfunction (CTCAE III-IV) - Patients on concurrent chemotherapy or interferon-alpha treatment - Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1: All patients will be evaluated extensively for toxicity using the CTCAE toxicity criteria and graft versus host disease criteria. Based on this dose-limiting toxicities will be scored. In case 1 patient will experience DLT at a particular dose, the cohort will be increased to 6 patients. The maximum tolerated IL-2 dose will be defined as the dose at which less than 2 patients experience DLT within a cohort of 6 patients. Phase 2: The primary endpoint of phase 2 of the study is to evaluate te effect of NK cells following adoptive transfer in combination with sc IL-2 on disease activity in patients with AML. Effect will be determined as a CR or PR according to ELN criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Evaluation of the in vivo lifespan and expansion potential of the NK cells following adoptive transfer, either with or without IL-2 administration. For phase 2: A positive expansion rate of the infused NK cells requires an absolute number of >= 100 donor-derived NK cells per µl blood at day +7 and/or +14. - Exploration of the functional activity of the donor NK cells in PB and BM, either with and without sc IL-2 administration using flow cytometry and CD107a (LAMP-1)-based degranulation and IFNy-secretion assays - Evaluation of IL-2 plasma levels and cytokine concentrations (IL-15, IL-7, IFN-γ, TNFa, IL-6) pre- and post infusion of IL-2, which will be correlated with absolute lymphocyte count and in vivo NK cells persistence and expansion - For phase 2: amount of patients eligible for allogeneic stem cell transplantation defined at day +28 | — |
Countries
Netherlands
Outcome results
None listed