Acute Myeloid LeukemiaNCT06885476
Infusion of Alloreactive nk Cells for Mrd-positive Aml Patients
A study testing Infusion of alloreactive NK cells in people with Acute Myeloid Leukemia and Minimal Residual Disease, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Minimal Residual Disease, Natural Killer Cell
- What is being tested?
- Infusion of alloreactive NK cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteItaly
- Study dates
- 22 Jan 2021to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Antonio Curti
Bologna, BO, 40138
Antonio Curti, +390512144074, antonio.curti2@unibo.it
About this study
Official title: Infusion of Alloreactive nk Cells for Acute Myeloid Leukemia Patients, Eligible for Allogeneic Stem Cell Transplantiation, With Persistent Minimal Residual Disease After Conventional Chemotherapy
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.
Read more
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.
- Being tested
- Infusion of alloreactive NK cells
- Medical subject headings
- Leukemia, Myeloid, Acute, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of alloreactive NK cellsBiological
Infusion of alloreactive NK cells for acute leukemia patients harboring minimal residual disease after conventional chemotherapy and prior to allogeneic stem cell transplantation
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: Infusion of alloreactive NK cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 48 months
Secondary outcomes (9)
Number of patients who achieve and maintain MRD negativity after infusion of alloreactive NK cells
Number of patients who achieve and maintain MRD negativity after infusion of alloreactive
Measured: 48 months
Number of patients who enter ASCT in MRD-negativity
Number of patients who enter ASCT in MRD-negativity
Measured: 48 months
Relapse-free survival (RFS) of patients infused with alloreactive NK cells
Relapse-free survival (RFS)of patients infused with alloreactive NK cells
Measured: 48 months
overall survival (OS) of patients infused with alloreactive NK cells
overall survival (OS) of patients infused with alloreactive NK cells
Measured: 48 months
Assess the predictive impact of donor NK cell repertoire on overall survival
Assess the predictive impact of donor NK cell repertoire as evaluated as the number of alloreactive NK cells/kg, in terms of overall survival
Measured: 48 months
Assess the predictive impact of donor NK cell repertoire on relapse-free survival
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
Measured: 48 months
Evaluate the microchimerism of patients receiving human NK cells
Evaluate the microchimerism of patients receiving human NK cells, as evaluated as percent of donor's cells into recipients
Measured: 48 months
Functionally evaluate, in vitro and ex vivo, the antitumor activity of infused NK cells
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).
Measured: 48 months
Assess the molecular features of infused NK cells
Assess the molecular features of infused NK cells, qualitative gene expression profile.
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2025
- Study start22 Jan 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antonio Curti, Principal investigator, Istituto di Ematologia Seràgnoli, Azienda Ospedaliero-Universitaria di Bologna (IRCCS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06885476
- Sponsor's protocol ID
- MRD-NK
- Status last verified
- Apr 2024
- First submitted
- 22 Jan 2021
- Last updated
- 20 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infusion of Alloreactive nk Cells for Acute Myeloid Leukemia Patients, Eligible for Allogeneic Stem Cell Transplantiation, With Persistent Minimal Residual Disease After Conventional Chemotherapy
- ClinicalTrials.gov ID
- NCT06885476
- Acronym / sponsor ID
- MRD-NK
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- 22 Jan 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 20 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Infusion of alloreactive NK cells | Experimental | Biological: Infusion of alloreactive NK cellsInfusion of alloreactive NK cells for acute leukemia patients, eligible for allogeneic stem cell transplantation, with persistent minimal residual disease after conventional chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Diagnosis of de novo or secondary AML
- Age ≥ 18 years
- Morphologic CR
- Eligibility for ASCT
- MRD-positivity after induction chemotherapy
Key exclusion criteria (6 listed)
- Diagnosis of AML FAB M3
- HIV positivity.
- HCV positivity with high viral load.
- Pregnant or nursing females.
- Current uncontrolled infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Infusion of alloreactive NK cellsInfusion of alloreactive NK cells for acute leukemia patients harboring minimal residual disease after conventional chemotherapy and prior to allogeneic stem cell transplantation | Biological | Infusion of alloreactive NK cells |
Primary outcome
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
Time frame: 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
Time frame: 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.
9 secondary outcomes
Number of patients who achieve and maintain MRD negativity after infusion of alloreactive NK cells
Time frame: 48 months
Number of patients who enter ASCT in MRD-negativity
Time frame: 48 months
Relapse-free survival (RFS) of patients infused with alloreactive NK cells
Time frame: 48 months
overall survival (OS) of patients infused with alloreactive NK cells
Time frame: 48 months
Assess the predictive impact of donor NK cell repertoire on overall survival
Time frame: 48 months
Assess the predictive impact of donor NK cell repertoire on relapse-free survival
Time frame: 48 months
Evaluate the microchimerism of patients receiving human NK cells
Time frame: 48 months
Functionally evaluate, in vitro and ex vivo, the antitumor activity of infused NK cells
Time frame: 48 months
Assess the molecular features of infused NK cells
Time frame: 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Antonio Curti principal investigator
Istituto di Ematologia Seràgnoli, Azienda Ospedaliero-Universitaria di Bologna (IRCCS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Infusion of alloreactive NK cells in people with Acute Myeloid Leukemia and Minimal Residual Disease, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Antonio Curti (+390512144074, antonio.curti2@unibo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 48 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2025; AzTrials last refreshed its copy on 7 Nov 2026.