CAR-NK Cells Production and Expansion From Patients With Lympho or Myeloproliferative Disorders and From Healthy Donors

NCT06727383 | Recruiting

• 1 other identifier: IEO 1886
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief 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, 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.

Conditions

Healthy Donors; Myeloproliferative Diseases; Lymphoproliferative Disorders

Keywords

CAR-NK cells; immunotherapeutic activity

Outcome Measures

Primary Outcomes (1)

• 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)

  3 years

Study Arms (3)

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.

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.

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

Procedure: leukapheresis

Interventions

peripheral blood collection PROCEDURE

standard blood test procedures

Cohort a; Cohort b

leukapheresis PROCEDURE

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.

Cohort c

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects over the age of 18 capable of understanding and willing
• Subjects affected by myelo/lymphoproliferative diseases

You may not qualify if:

• 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

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

Istituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

MeSH Terms

Conditions

Lymphoproliferative Disorders

Interventions

Leukapheresis

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Enrico Derenzini, MD

  Istituto Europeo di Oncologia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Enrico Derenzini

CONTACT

+390257489538; enrico.derenzini@ieo.it

Fulvia Fusar

CONTACT

+390257489538; fulvia.fusarimperatore@ieo.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2024
• First Posted: December 10, 2024
• Study Start: December 21, 2022
• Primary Completion: December 21, 2025
• Study Completion: December 21, 2025
• Last Updated: December 10, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)