Healthy DonorsNCT06727383
CAR-NK Cells Production and Expansion From Patients With Lympho or Myeloproliferative Disorders and From Healthy Donors
A study testing peripheral blood collection and leukapheresis in people with Healthy Donors and Myeloproliferative Diseases, run by European Institute of Oncology at 1 site in Italy.
Trial summary
Recent studies demonstrated the safety and efficacy of allogeneic and autologous infusion of NK cells as adoptive immunotherapy in malignant hematological diseases and solid tumors.NK cells are innate immunity effectors with antitumor activity regulated by a wide variety of receptors located on their cell surface… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy Donors, Myeloproliferative Diseases, Lymphoproliferative Disorders
- What is being tested?
- peripheral blood collection and leukapheresis
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteItaly
- Study dates
- 21 Dec 2022to 21 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects over the age of 18 capable of understanding and willing
- Subjects affected by myelo/lymphoproliferative diseases
Who cannot join
- Patients with psychiatric, addictive, or any disorder, which compromises ability to give informed consent for participation in this study.
- Patients affected by lympho or myeloproliferative disorders and Healthy Donors with known acute and chronic viral and bacterial infections :HIV, HCV (Hepatitis C Virus), HBV (Hepatitis B Virus), syphilis
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Istituto Europeo di Oncologia
Milan, 20141
Enrico Derenzini, +390257489538, enrico.derenzini@ieo.it
About this study
Official title: Production and Expansion of Chimeric Antigen Receptor (CAR)-Natural Killer (NK) Cells From Patients Affected by Lympho or Myeloproliferative Disorders and From Healthy Donors
Recent studies demonstrated the safety and efficacy of allogeneic and autologous infusion of NK cells as adoptive immunotherapy in malignant hematological diseases and solid tumors.NK cells are innate immunity effectors with antitumor activity regulated by a wide variety of receptors located on their cell surface, with both activating and inhibiting roles.Receptors with an inhibitory role include receptors of the KIRs family (Killer Immunoglobulin like Receptors) and receptors of the CD94 / NKG2A complex and are capable of recognizing molecules of Human Leukocyte Antigen class I (HLA-I). Receptors of the KIRs family are members of the immunoglobulin superfamily and are encoded by highly polymorphic genes located on chromosome 19q13.4 in a region known as a leukocyte receptor cluster (LCR). The predominant ligand for KIRs receptors is HLA-C, but other studies show that HLA-A and HLA-B are also involved. Receptors with an activating role, on the other hand, such as NCRs (Natural Cytotoxic receptors), are specific to NK cells, while other epitopes such as CD 56 are also present on other populations of T lymphocytes.
This receptor condition allows, in patients suffering from haemopathy and undergoing transplantation allogeneic stem cell, an alloreactivity induced by the mismatch between the donor's KIRs and their ligands on recipient target cells and, therefore, the role of NK cells as allogeneic effectors. The engraftment of NK cells has been shown to be correlated with a lower risk of disease recurrence, therefore the therapeutic infusion of NK cells from donors could allow, with benefit, the acquisition of fully functional NK cells in the recipient.
Read the detailed description
The primary aim of the study is to manufacture and expand NK cells expressing CD19, CD79 and CD123 CARs from Peripheral Blood Mononucleated Cells (PBMCs) (cohort a) and from CD34+ cells (cohort b and c) of subjects affected by myelo or lymphoproliferative disorders or healthy donors.
The secondary aim is to evaluate their cytotoxic activity in preclinical models. The main steps of CAR-NK cell manufacturing and preparation are the followings
- Collection of peripheral venous blood (40 mL collected in EDTA tubes for cohort a, or 10 mL from patients with >20 CD34+ cells/mcL for cohort b), or blood from bone marrow aspiration (5 mL of bone marrow collected in one EDTA tube for cohort b), or a part of LP (2 mL of PL in one EDTA tube for cohort c) from subjects with myelo/lymphoproliferative diseases and from Healthy Donors;
- Selection of mononucleated cells through a density gradient centrifugation technique (Ficoll-Histopaque) (cohort a and b);
- Selection of CD34 + Hematopoietic stem cells (HSCs) through magnetic activated cell sorting (cohort b)
- Expansion NK cells from PBMCs (cohort a), using supplements such as recombinant cytokines, stimulatory antibodies, medicinal products and irradiated cells to support the process;
- Expansion of CD34+ cells (cohort b and c), using supplements such as recombinant cytokines, stimulatory antibodies, medicinal products and irradiated cells to support the process, in order to promote differentiation to the NK cell lineage;
- Engineering of NK cells through retroviral or lentiviral vectors (VL) that enable transduction with chimeric antigen receptors (CARs) specific for neoplastic cells.
- Increasing the activation of NK cells through the down regulation of their inhibitory receptors (CRISPR Cas-9 technology and pharmacological modulation) or pharmacologic modulation of epigenetic, metabolic (HIF1-alpha) and immune-related pathways;
- Testing, in in vitro and in vivo preclinical models, the persistence and the activity of the CAR-NK cells produced.
100 patients and 40 healthy donors will be prospectively enrolled over 3 years in order to perform 70 experiments of NK-cell expansion from PBMCs and 70 experiments from CD34+ cells (from PB or bone marrow or LP).
- Being tested
- peripheral blood collection, leukapheresis
- Keywords
- CAR-NK cells, immunotherapeutic activity
- Medical subject headings
- Lymphoproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
peripheral blood collectionProcedure or surgery
standard blood test procedures
leukapheresisProcedure or surgery
Leukapheresis is the procedure that allows the separation and collection of hematopoietic stem cells (HSCs) from peripheral blood. The collection takes place through a machine called a "cell separator": it uses centrifugal force to separate the mononuclear cells from all the other cells in the blood and plasma.
| Study group | Role | What they receive |
|---|---|---|
| Cohort a | Experimental | The collection of PBMCs will be performed during standard blood test procedures: 40 mL of PB will be collected in 8 EDTA tubes. Receives: Procedure: peripheral blood collection |
| Cohort b | Experimental | The collection of CD34+ cells will be performed during HSC mobilization and staging bone marrow aspirations, as follows:
1. During standard HSC mobilization, 10 mL peripheral blood will be collected in two EDTA tubes from patients with >20 CD34+ cells/mcL.
2. 5 mL of bone marrow will be collected in one EDTA tube during bone marrow aspiration performed in the context of standard diagnostic procedures. Receives: Procedure: peripheral blood collection |
| Cohort c | Experimental | The collection of CD34+ cells will be performed from a LP required in the context of standard therapeutic procedures Receives: Procedure: leukapheresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary objective
100 patients and 40 healthy donors will be prospectively enrolled over 3 years in order to perform 70 experiments of NK-cell expansion from PBMCs and 70 experiments from CD34+ cells (from PB or bone marrow or LP). We aim to demonstrate feasibility of the program (as defined in the primary endpoint) in 80% of eligible patients in the cohorts a), b) and c). The study will be powered to estimate the fraction of enrolled patients that obtain a full NK expansion defined as A) ≥40 fold ex-vivo expansion of the NK cell population at day 15 of cell culture and B) ≥1x10^9 NK-cells following ex-vivo expansion of 1x10^6 CD34+ cells at day 30 of cell culture; a minimum of 70 patients are required to estimate a true prevalence rate between 70 and 90% with 95% confidence interval (with 56 expected successful cases)
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2024
- Study start21 Dec 2022
- Primary completion21 Dec 2025 (estimated)
- Study completion21 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy DonorsStudies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Enrico Derenzini, MD, Principal investigator, Istituto Europeo di Oncologia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06727383
- Sponsor's protocol ID
- IEO 1886
- Status last verified
- Mar 2024
- First submitted
- 19 Mar 2024
- Last updated
- 10 Dec 2024
- 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 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Production and Expansion of Chimeric Antigen Receptor (CAR)-Natural Killer (NK) Cells From Patients Affected by Lympho or Myeloproliferative Disorders and From Healthy Donors
- ClinicalTrials.gov ID
- NCT06727383
- Acronym / sponsor ID
- IEO 1886
- Keywords
- CAR-NK cells, immunotherapeutic activity
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- 21 Dec 2022 (actual)
- Primary completion
- 21 Dec 2025 (estimated)
- Study completion
- 21 Dec 2025 (estimated)
- First posted
- 10 Dec 2024 (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.
Recent studies demonstrated the safety and efficacy of allogeneic and autologous infusion of NK cells as adoptive immunotherapy in malignant hematological diseases and solid tumors.NK cells are innate immunity effectors with antitumor activity regulated by a wide variety of receptors located on their cell surface, with both activating and inhibiting roles.Receptors with an inhibitory role include receptors of the KIRs family (Killer Immunoglobulin like Receptors) and receptors of the CD94 / NKG2A complex and are capable of recognizing molecules of Human Leukocyte Antigen class I (HLA-I). Receptors of the KIRs family are members of the immunoglobulin superfamily and are encoded by highly polymorphic genes located on chromosome 19q13.4 in a region known as a leukocyte receptor cluster (LCR). The predominant ligand for KIRs receptors is HLA-C, but other studies show that HLA-A and HLA-B are also involved. Receptors with an activating role, on the other hand, such as NCRs (Natural Cytotoxic receptors), are specific to NK cells, while other epitopes such as CD 56 are also present on other populations of T lymphocytes.
This receptor condition allows, in patients suffering from haemopathy and undergoing transplantation allogeneic stem cell, an alloreactivity induced by the mismatch between the donor's KIRs and their ligands on recipient target cells and, therefore, the role of NK cells as allogeneic effectors. The engraftment of NK cells has been shown to be correlated with a lower risk of disease recurrence, therefore the therapeutic infusion of NK cells from donors could allow, with benefit, the acquisition of fully functional NK cells in the recipient.
Detailed description
The primary aim of the study is to manufacture and expand NK cells expressing CD19, CD79 and CD123 CARs from Peripheral Blood Mononucleated Cells (PBMCs) (cohort a) and from CD34+ cells (cohort b and c) of subjects affected by myelo or lymphoproliferative disorders or healthy donors.
The secondary aim is to evaluate their cytotoxic activity in preclinical models. The main steps of CAR-NK cell manufacturing and preparation are the followings
- Collection of peripheral venous blood (40 mL collected in EDTA tubes for cohort a, or 10 mL from patients with >20 CD34+ cells/mcL for cohort b), or blood from bone marrow aspiration (5 mL of bone marrow collected in one EDTA tube for cohort b), or a part of LP (2 mL of PL in one EDTA tube for cohort c) from subjects with myelo/lymphoproliferative diseases and from Healthy Donors;
- Selection of mononucleated cells through a density gradient centrifugation technique (Ficoll-Histopaque) (cohort a and b);
- Selection of CD34 + Hematopoietic stem cells (HSCs) through magnetic activated cell sorting (cohort b)
- Expansion NK cells from PBMCs (cohort a), using supplements such as recombinant cytokines, stimulatory antibodies, medicinal products and irradiated cells to support the process;
- Expansion of CD34+ cells (cohort b and c), using supplements such as recombinant cytokines, stimulatory antibodies, medicinal products and irradiated cells to support the process, in order to promote differentiation to the NK cell lineage;
- Engineering of NK cells through retroviral or lentiviral vectors (VL) that enable transduction with chimeric antigen receptors (CARs) specific for neoplastic cells.
- Increasing the activation of NK cells through the down regulation of their inhibitory receptors (CRISPR Cas-9 technology and pharmacological modulation) or pharmacologic modulation of epigenetic, metabolic (HIF1-alpha) and immune-related pathways;
- Testing, in in vitro and in vivo preclinical models, the persistence and the activity of the CAR-NK cells produced.
100 patients and 40 healthy donors will be prospectively enrolled over 3 years in order to perform 70 experiments of NK-cell expansion from PBMCs and 70 experiments from CD34+ cells (from PB or bone marrow or LP).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort a | Experimental | Procedure: peripheral blood collectionThe collection of PBMCs will be performed during standard blood test procedures: 40 mL of PB will be collected in 8 EDTA tubes. |
| Cohort b | Experimental | Procedure: peripheral blood collectionThe collection of CD34+ cells will be performed during HSC mobilization and staging bone marrow aspirations, as follows: 1. During standard HSC mobilization, 10 mL peripheral blood will be collected in two EDTA tubes from patients with >20 CD34+ cells/mcL. 2. 5 mL of bone marrow will be collected in one EDTA tube during bone marrow aspiration performed in the context of standard diagnostic procedures. |
| Cohort c | Experimental | Procedure: leukapheresisThe collection of CD34+ cells will be performed from a LP required in the context of standard therapeutic procedures |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects over the age of 18 capable of understanding and willing
- Subjects affected by myelo/lymphoproliferative diseases
Key exclusion criteria (2 listed)
- Patients with psychiatric, addictive, or any disorder, which compromises ability to give informed consent for participation in this study.
- Patients affected by lympho or myeloproliferative disorders and Healthy Donors with known acute and chronic viral and bacterial infections :HIV, HCV (Hepatitis C Virus), HBV (Hepatitis B Virus), syphilis
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 |
|---|---|---|
| peripheral blood collectionstandard blood test procedures | Procedure or surgery | Cohort a, Cohort b |
| leukapheresisLeukapheresis is the procedure that allows the separation and collection of hematopoietic stem cells (HSCs) from peripheral blood. The collection takes place through a machine called a "cell separator": it uses centrifugal force to separate the mononuclear cells from all the other cells in the blood and plasma. | Procedure or surgery | Cohort c |
Primary outcome
Primary objective
Time frame: 3 years
100 patients and 40 healthy donors will be prospectively enrolled over 3 years in order to perform 70 experiments of NK-cell expansion from PBMCs and 70 experiments from CD34+ cells (from PB or bone marrow or LP). We aim to demonstrate feasibility of the program (as defined in the primary endpoint) in 80% of eligible patients in the cohorts a), b) and c). The study will be powered to estimate the fraction of enrolled patients that obtain a full NK expansion defined as A) ≥40 fold ex-vivo expansion of the NK cell population at day 15 of cell culture and B) ≥1x10^9 NK-cells following ex-vivo expansion of 1x10^6 CD34+ cells at day 30 of cell culture; a minimum of 70 patients are required to estimate a true prevalence rate between 70 and 90% with 95% confidence interval (with 56 expected successful cases)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2024.
- 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. This study is not recruiting at the moment.
Enrico Derenzini, MD principal investigator
Istituto Europeo di Oncologia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing peripheral blood collection and leukapheresis in people with Healthy Donors and Myeloproliferative Diseases, run by European Institute of Oncology 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 2 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 10 Dec 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Enrico Derenzini (+390257489538, enrico.derenzini@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary objective (time frame: 3 years). 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 10 Dec 2024.