Natural Killer Cell Immunotherapy in Combination With PARP-inhibition in Acute Myeloid Leukemia
Status:
Not yet recruiting
Trial end date:
2026-01-01
Target enrollment:
Participant gender:
Summary
Therapy resistance remains the major obstacle to cure in many types of cancer. In particular
in leukemia, therapy resistance depends on leukemic stem cells (LSC) that exhibit inherent
therapy resistance to multiple drugs and contribute to overt leukemic relapse. Cellular
therapies alone or in combination with other targeted or chemotherapeutic approaches can
overcome drug mediated therapy resistance and induce long lasting remissions. Several trials
have shown that adoptive transfer of allogeneic NK cells can induce clinical remission in
patients with myeloid malignancies. In addition, the antileukemic efficacy of alloreactive NK
cells has been shown to facilitate cure after T cell depleted haploidentical stem cell
transplantation. Recently, it was demonstrated that absence of NKGD2 ligand expression on
leukemic stem cells determines therapy resistance and immune escape towards NK cells in AML.
PARP1 inhibitors can induce re-expression of NKG2D ligands. This phase I/II clinical trial
will evaluate the combination of NK cell therapy and PARP inhibition by Talazoparib in
patients with poor prognosis AML as characterized by Minimal Residual Disease (MRD) or overt
relapse with less than 20% bone marrow blasts. The hypothesis that allogeneic NK cell therapy
combined with PARP inhibition will increase the response rate (CR/CRi for relapsed/
refractory patients and MRD-response for MRD positive patients) from 35% to 60% will be
tested. The co-primary endpoints are i) response to treatment defined as complete remission
(CR) for patients with overt leukemia at time of inclusion and MRD decrease >1log10 for
patients with rising MRD at time of inclusion as well as ii) safety and feasibility of the
protocol. Key secondary endpoints are event free survival and overall survival. Two cohorts
will be assessed independently: patients with i) overt leukemia and ii) patients with rising
MRD at time of inclusion. Safety and feasibility will be analyzed continuously during the
entire trial. The NAKIP-AML trial will analyze efficacy and feasibility of NK cell
transplantation together with PARP1 inhibition.