Infusion of ex vivo-generated allogeneic natural killer cells in combination with subcutaneous IL-2 in patients with acute myeloid leukemia: a phase I/IIa study*

Recruiting

Conditions: Acute myeloid leukemia
10024324

Registration Number: NL-OMON55708

Lead Sponsor: Radboud Universitair Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 23

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

- 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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase 1: All patients will be evaluated extensively for toxicity using the<br /><br>CTCAE toxicity criteria and graft versus host disease criteria. Based on this<br /><br>dose-limiting toxicities will be scored. In case 1 patient will experience DLT<br /><br>at a particular dose, the cohort will be increased to 6 patients. The maximum<br /><br>tolerated IL-2 dose will be defined as the dose at which less than 2 patients<br /><br>experience DLT within a cohort of 6 patients.<br /><br><br /><br>Phase 2: The primary endpoint of phase 2 of the study is to evaluate te effect<br /><br>of NK cells following adoptive transfer in combination with sc IL-2 on disease<br /><br>activity in patients with AML. Effect will be determined as a CR or PR<br /><br>according to ELN criteria.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Evaluation of the in vivo lifespan and expansion potential of the NK cells<br /><br>following adoptive transfer, either with or without IL-2 administration. For<br /><br>phase 2: A positive expansion rate of the infused NK cells requires an absolute<br /><br>number of >= 100 donor-derived NK cells per µl blood at day +7 and/or +14.<br /><br>- Exploration of the functional activity of the donor NK cells in PB and BM,<br /><br>either with and without sc IL-2 administration using flow cytometry and CD107a<br /><br>(LAMP-1)-based degranulation and IFNy-secretion assays<br /><br>- Evaluation of IL-2 plasma levels and cytokine concentrations (IL-15, IL-7,<br /><br>IFN-γ, TNFa, IL-6) pre- and post infusion of IL-2, which will be correlated<br /><br>with absolute lymphocyte count and in vivo NK cells persistence and expansion<br /><br>- For phase 2: amount of patients eligible for allogeneic stem cell<br /><br>transplantation defined at day +28</p><br>