Infusion of Alloreactive nk Cells for Mrd-positive Aml Patients

NCT06885476 | Recruiting

• 1 other identifier: MRD-NK
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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

  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)

  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

  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.

  48 months

Secondary Outcomes (9)

• Number of patients who achieve and maintain MRD negativity after infusion of alloreactive NK cells

  48 months

• Number of patients who enter ASCT in MRD-negativity

  48 months

• Relapse-free survival (RFS) of patients infused with alloreactive NK cells

  48 months

• overall survival (OS) of patients infused with alloreactive NK cells

  48 months

• Assess the predictive impact of donor NK cell repertoire on overall survival

  48 months

Study Arms (1)

Infusion of alloreactive NK cells

EXPERIMENTAL

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

Biological: Infusion of alloreactive NK cells

Interventions

Infusion of alloreactive NK cells BIOLOGICAL

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

Infusion of alloreactive NK cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead

Study Sites (1)

Antonio Curti

Bologna, BO, 40138, Italy

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasm, Residual

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Antonio Curti

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonio Curti

CONTACT

+390512144074; antonio.curti2@unibo.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2021
• First Posted: March 20, 2025
• Study Start: January 22, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 20, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)