Infusion of Alloreactive nk Cells for Mrd-positive Aml Patients

Not Applicable

Recruiting

• Conditions: Acute Myeloid Leukemia; Minimal Residual Disease; Natural Killer Cell
• Interventions: Biological: Infusion of alloreactive NK cells

• Registration Number: NCT06885476
• Lead Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Brief Summary

This is a interventional, transplantation study. The procedure under study is the infusion of alloreactive NK cells in adult AML patients, eligible for ASCT, who achieved CR after conventional chemotherapy, but harbor MRD-positivity.

Haploidentical KIR-L mismatched donors will be included if present at least one allele mismatch at a class I locus among the following ones: HLA-C alleles with Asn77-Lys80, HLA-C alleles with Ser77-Asn80, HLA-Bw4 alleles. KIR-L mismatched donor alloreactive NK cell repertoire will be evaluated in order to determine the functional cell dose to be used for NK cell collection. Phenotypical analysis of KIRs will be correlated to functional tests. NK cells will be selected from a steady-state large volume leukapheresis product from a suitable haploidentical KIR-ligand incompatible donor. NK cell purification will be performed if the donor leukapheresis product contains at least 10x106 NK cells/Kg.

Immunomagnetic enrichment of NK cells will follow two subsequent steps: 1) depletion of CD3+ T cells followed by 2) positive selection of CD56+ NK cells.

Patients will receive immunosuppressive chemotherapy, fludarabine (Flu) 25 mg/mq/ from day -5 to -3 and cyclophosphamide (Cy) 2 g/mq on day -2 (Flu/Cy). Two days after Cy administration, patients will be infused intravenously with a single dose of cryopreserved NK cells (day 0), which will be followed by subcutaneous administration of IL-2 (10 x 106 IU/day, 3 times weekly) for 2 weeks (6 doses total). PB samples will also be collected for biological studies. In particular, PB samples will be collected for molecular assessment of microchimerism and tracking of haploidentical NK cells for 30 days, immunophenotype studies, alloreactive NK cells cloning and functional assays (cytotoxicity). Enrolled patients will be followed up for at least 12 months after NK cell infusion.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-22
• Study First Submitted: 2021-01-22
• Status Verified: 2024-04
• Study First Submitted QC: 2025-03-18
• Last Update Submitted: 2025-03-18
• Study First Posted: 2025-03-20
• Last Update Posted: 2025-03-20
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Diagnosis of de novo or secondary AML
• Age ≥ 18 years
• Morphologic CR
• Eligibility for ASCT
• MRD-positivity after induction chemotherapy
• Availability of a KIR-L incompatible haploidentical donor
• Performance Status ≥ 70% (Karnofsky score) or ≤ 2 (WHO).
• Adequate renal (serum creatinine < 2 mg/dl), pulmonary (Sat O2 ≥ 96%) and hepatic (ALT/AST < 2.5 x N) function.
• Left Ventricular Ejection Fraction (LVEF) of >50% as determined by Echocardiogram (ECHO).
• Signed informed consent.

Exclusion Criteria

• Diagnosis of AML FAB M3
• HIV positivity.
• HCV positivity with high viral load.
• Pregnant or nursing females.
• Current uncontrolled infection.
• Signs or symptoms of fluid retention (e.g. pleural effusion).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Infusion of alloreactive NK cells	Infusion of alloreactive NK cells	Infusion of alloreactive NK cells for acute leukemia patients, eligible for allogeneic stem cell transplantation, with persistent minimal residual disease after conventional chemotherapy

Primary Outcome Measures

Name	Time	Method
Safety of infusing a functional target cell dose of 2x105 alloreactive NK cells/kg in AML patients,eligible for ASCT, with persistent MRD after conventional chemotherapy	48 months	Safety of infusing a functional target cell dose of 2x105 alloreactive NK cells/kg in AML patients,eligible for ASCT, with persistent MRD after conventional (number of adverse events and severe adverse events)
Feasibility of collecting a functional target cell dose of 2x105 alloreactive NK cells/kg in at least 70% of patients entering the study	48 months	Feasibility of collecting a functional target cell dose of 2x105 alloreactive NK cells/kg in at least 70% of patients entering the study as evaluated by in vitro cytotoxicity assay.

Secondary Outcome Measures

Name	Time	Method
Number of patients who achieve and maintain MRD negativity after infusion of alloreactive NK cells	48 months	Number of patients who achieve and maintain MRD negativity after infusion of alloreactive
Number of patients who enter ASCT in MRD-negativity	48 months	Number of patients who enter ASCT in MRD-negativity
Relapse-free survival (RFS) of patients infused with alloreactive NK cells	48 months	Relapse-free survival (RFS)of patients infused with alloreactive NK cells
overall survival (OS) of patients infused with alloreactive NK cells	48 months	overall survival (OS) of patients infused with alloreactive NK cells
Assess the predictive impact of donor NK cell repertoire on overall survival	48 months	Assess the predictive impact of donor NK cell repertoire as evaluated as the number of alloreactive NK cells/kg, in terms of overall survival
Assess the predictive impact of donor NK cell repertoire on relapse-free survival	48 months	Assess the predictive impact of donor NK cell repertoire as evaluated as the number of alloreactive NK cells/kg, in terms of relapse-free survival
Evaluate the microchimerism of patients receiving human NK cells	48 months	Evaluate the microchimerism of patients receiving human NK cells, as evaluated as percent of donor's cells into recipients
Functionally evaluate, in vitro and ex vivo, the antitumor activity of infused NK cells	48 months	Functionally evaluate, in vitro and ex vivo, the antitumor activity of infused NK cells, as evaluated by in vitro cytotoxicity assay (percent of lysis by donor NK cells of recipients cells).
Assess the molecular features of infused NK cells	48 months	Assess the molecular features of infused NK cells, qualitative gene expression profile.

Trial Locations

Locations (1)

Antonio Curti; 🇮🇹 Bologna, BO, Italy