atural killer cellen tegen acute myeloïde leukemie

Recruiting

Conditions: Acute myeloid leukemia and Myelodysplastic syndrome with excess of blasts 2

Registration Number: NL-OMON25848

Lead Sponsor: Radboudumc

Brief Summary: https://www.ntvh.nl/journal-article/nk4aml-toediening-van-ex-vivo-gegenereerde-allogene-natural-killer-cellen-in-combinatie-met-subcutaan-il-2-bij-patienten-met-acute-myeloide-leukemie/

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 23

Inclusion Criteria

Newly diagnosed AML or MDS EB-2 defined according to WHO 2016 criteria; AML may be secondary to prior hematological disorders, including MDS, and/or therapy-related.
- Stable or at least non-rapidly progressive disease with or without disease controlling medication.
- Patients may belong to any of the following categories:
o Relapsed/refractory disease after treatment with intensive chemotherapy, hypomethylating agents, targeted agents, autologous or allo-SCT (at least 6 months ago) and DLI
o Newly diagnosed, untreated patients ineligible for allo-SCT
- Age = 18 years
- WHO performance 0- 2 (Appendix 2)
- Life expectancy of > 4 months
- Written informed consent
- Hydrea is allowed as pre-treatment to control blast count until day -3
- Hypomethylating agents decitabine or azacitidine are allowed until day -7

Exclusion Criteria

- Rapid-progressive disease in case of previous therapy (see Appendix 1).
- Patients on immunosuppressive drugs or active GvHD
- Patients with active infections (viral, bacterial or fungal); acute anti-infectious therapy must have been completed within 14 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)
- Presence of anti-HLA class I antibodies
- 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
The study is divided in two phases.<br>The primary objective of phase I of the study is to evaluate the safety and toxicity of the infusion of ex vivo-expanded UCB-NK cells, both with and without SC IL-2, following a non-myeloablative immunosuppressive conditioning regimen in patients with AML or MDS with excess blasts-2 (EB-2).<br><br>The primary objective of phase IIa of the study is to evaluate the effect of UCB-NK cell adoptive immunotherapy in combination with SC IL-2 following a non-myeloablative immunosuppressive conditioning regime on disease activity in patients with AML/MDS-EB-2.

Secondary Outcome Measures

Name	Time	Method
For both phases of the study secondary objectives include 1) evaluation of the in vivo lifespan and expansion potential of the donor NK cells following adoptive transfer, 2) exploration of the functional activity of the donor NK cells in peripheral blood (PB) and bone marrow (BM) and 3) evaluation of IL-2 serum levels and plasma cytokine concentrations pre- and post-administration of SC IL-2. An extra secondary objective for the phase IIa of the study is the number of patients bridged to transplant with this treatment protocol.