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NOT YET RECRUITING
NCT05319249
PHASE1/PHASE2

Natural Killer Cell Immunotherapy in Combination With PARP-inhibition in Acute Myeloid Leukemia

Sponsor: German Cancer Research Center

View on ClinicalTrials.gov

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.

Official title: Natural Killer Cell Immunotherapy in Combination With PARP-inhibition to Overcome NKG2D Mediated Immune Evasion in Acute Myeloid Leukemia

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

54

Start Date

2024-06

Completion Date

2028-06

Last Updated

2024-04-05

Healthy Volunteers

No

Interventions

BIOLOGICAL

NK cells

NK cells will be given as a single intravenous infusion.

DRUG

Talazoparib 1 MG [Talzenna]

Subjects will receive treatment with Talazoparib capsules 1 mg/day (4 days) with subsequent intravenous NK cell infusion.