Infusion of Alloreactive nk Cells for Mrd-positive Aml Patients

NCT ID: NCT06885476

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-22
• Study Completion Date: 2026-12-31

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.

Conditions

Acute Myeloid Leukemia; Minimal Residual Disease; Natural Killer Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Infusion of alloreactive NK cells

Intervention Type: BIOLOGICAL

Infusion of alloreactive NK cells for acute leukemia patients harboring minimal residual disease after conventional chemotherapy and prior to allogeneic stem cell transplantation

Interventions

Infusion of alloreactive NK cells

Infusion of alloreactive NK cells for acute leukemia patients harboring minimal residual disease after conventional chemotherapy and prior to allogeneic stem cell transplantation

Intervention Type: BIOLOGICAL

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Azienda Ospedaliero-Universitaria di Bologna

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Curti

Role: PRINCIPAL_INVESTIGATOR

Istituto di Ematologia Seràgnoli, Azienda Ospedaliero-Universitaria di Bologna (IRCCS)

Locations

Antonio Curti

Bologna, BO, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Antonio Curti

Role: CONTACT

antonio.curti2@unibo.it

+390512144074

Facility Contacts

Antonio Curti

Role: primary

antonio.curti2@unibo.it

+390512144074

Other Identifiers

MRD-NK

Identifier Type: -

Identifier Source: org_study_id