Natural Killer-cell Therapy for Acute Myeloid Leukemia (NK4AML)
Acute Myeloid Leukemia Refractory, Acute Myeloid Leukemia, Relapsed, Adult
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia Refractory focused on measuring Natural Killer cells, Acute Myeloid Leukemia, Cellular Immunotherapy
Eligibility Criteria
Inclusion Criteria:
- AML patients (de novo and secondary) or patients with MDS excess blasts-2 according to WHO criteria 2016, who have stable disease or non-rapidly progressive disease with or without disease controlling medication who are (at time of inclusion) ineligible for allo-SCT.
Patients may belong to any of the following categories:
- Relapsed/refractory disease after treatment with intensive chemotherapy, hypomethylating agents, targeted agents, autologous or allo-SCT (at least 6 months ago) and DLI
- Newly diagnosed, untreated patients ineligible for allo-SCT
Other inclusion criteria:
- 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 according to ELN criteria 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 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
Sites / Locations
- Radboud University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Active Comparator
Active Comparator
NK cells without IL-2
NK cells with low dose IL-2
NK cells with higher dose IL-2
On day 0, patients will receive a fixed dose of 1.0-3.0 x 10^9 allogeneic UCB-NK cells. Prior to NK cell infusion, patients will receive cyclophosphamide and fludarabine (Cy/Flu) based lymphodepleting chemotherapy. NK cells administration will not be followed by sc IL-2. N=3.
On day 0, patients will receive a fixed dose of 1.0-3.0 x 10^9 allogeneic UCB-NK cells. Prior to NK cell infusion, patients will receive cyclophosphamide and fludarabine (Cy/Flu) based lymphodepleting chemotherapy. IL-2 will be administered in a fixed dose of 3.0 x 10^6 units starting 4 hours after NK cell infusion and given every other day for 6 doses in total. N=3
On day 0, patients will receive a fixed dose of 1.0-3.0 x 10^9 allogeneic UCB-NK cells. Prior to NK cell infusion, patients will receive cyclophosphamide and fludarabine (Cy/Flu) based lymphodepleting chemotherapy. IL-2 will be administered in a fixed dose of 6.0 x 10^6 units starting 4 hours after NK cell infusion and given every other day for 6 doses in total. N=6