AML patients who do not have rapid progressive disease with or without disease controlling medication and who are not eligible for allogeneic SCT.
Conditions
Interventions
Product Name: Ex-vivo generated allogeneic RNK001 NK cells
Product Code: x
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: EX VIVO-GENERATED ALLOGENEIC RNK001 NK CELLS
Current Sponsor
Sponsors
Radboud University Medical Centre
Eligibility
Sex/Gender
All
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 19
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 |
|---|---|
| Main Objective: The study is divided in two phases. The primary objective of phase I of the study is to evaluate the safety and toxicity of the infusion of RNK001 NK cells, both with and without sc IL-2 following immunosuppressive conditioning therapy in patients with AML. In this phase we will determine the maximum tolerable dose of IL-2. The primary objective of phase II of the study is to evaluate the effect of NK cell adoptive immunotherapy in combination with sc IL-2 on disease activity in patients with AML. ;Secondary Objective: For both phases of the study secondary objectives are evaluation of the in vivo lifespan and expansion potential of the RNK001 NK cells following adoptive transfer, exploration of the functional activity of the donor RNK001 NK cells in peripheral blood (PB) and bone marrow (BM) and evaluation of IL-2 serum levels and cytokine concentration pre- and post infusion of IL-2. For phase II of the study also the amount of patients eligible for allogeneic stem cell transplantation will be determined.;Primary end point(s): 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 <2 patients experience DLT within a cohort of 6 patients. Phase 2: The primary endpoint of phase 2 of the study is to evaluate the effect of RNK001 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. ;Timepoint(s) of evaluation of this end point: Phase 1: DLT’s will be monitored till 28 days (4 weeks) after NK cell infusion. Four weeks after NK cell infusion of the last patient in a cohort, the next patient can be included in a new cohort. Pha | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 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-?, 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 - Amount of patients eligible for allogeneic stem cell transplantation (phase II only).;Timepoint(s) of evaluation of this end point: 1 year after completion of the study | — |
Countries
Netherlands
Contacts
Public ContactProject leader
Radboud University Medical Centre
Outcome results
None listed