Phase I of Infusion of Selected Donor NK Cells After Allogeneic Stem Cell Transplantation (DLI-NK)

April 16, 2026 updated by: Institut Paoli-Calmettes

Phase I of Infusion of Selected Donor NK Cells After HLA Identical Allogeneic Stem Cell Transplantation Prepared With Reduced Intensity Conditioning - DLI-NK/IPC 2012-003

The goal of our study will be to determine the clinical and biological safety of infusing immuno-selected NK (Natural Killer) CD3-/CD56+ cells, early after allogeneic transplantation with colony stimulating factor (G-CSF) mobilized peripheral blood stem cells and Reduced Intensity Conditioning (RIC), as a potential substitute to usual "Donor Lymphocyte Infusion" (DLI), that contain the whole range of immune effectors. The trial will include several progressive steps: dose escalation up to a level compatible with the cost-effectiveness potential of the device and clinical situation and recombinant interleukin-2 (r-IL2) activation of selected NK cells in vitro prior to re-infusion.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the mid 90's, it has been shown that donor lymphocyte infusions (DLI), when given for Chronic Myelocytic Leukemia (CML) that has relapsed after conventional allogeneic stem cell transplantation (SCT), result in a high incidence of durable cytogenetic and molecular remissions. However, regular documented effects are the occurrence of secondary aplasia and/or graft-versus-host disease (GVHD) including the post RIC situation. These effects are related to the high content of cytotoxic T cells in the DLI. Attempts to deplete CD8+ T-cells from DLI have been conducted with promising results but are not totally satisfactory.

More recently the infusion of r-IL2 ex-vivo activated autologous or allogeneic NK-selected cells have been studied and the safety established in patients presenting various malignancies.

Indeed, NK are thoroughly characterized in terms of genotype, phenotype and function. Although a handful of clinical-grade reagents and devices exist that give access to the human NK cell compartment, an immuno-selection device exists that allows for the selection of NK cells from various types of hematopoietic cell collections in view of clinical applications: the process produces CD3-/CD56+ cells in two steps and have been used in the previous experiences.

Study Type

Interventional

Enrollment (Estimated)

17

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France, 13009
        • Institut Paoli-Calmettes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patient treated with allogeneic stem cell transplantation

    • Presenting an hematological malignancy with an intermediate, high or very high risk index according to the disease risk index developed by the Dana Farber Cancer Institute
    • Donor: HLA matched related or unrelated (10/10) donor
    • Graft: Peripheral stem cell transplant
    • Reduced Intensity Conditioning as used in the current transplant program: Fludarabine, IV Busulfan and Thymoglobuline
  2. Age above 18 and under 70
  3. Eastern Cooperative Oncology Group (ECOG) 0-1 or Karnofsky index ≥ 70 %
  4. Survival expectation > 6 months
  5. Affiliation to social security
  6. Signed informed consent from Donor and Patient

Exclusion Criteria:

  1. Active grade >= 2 acute GVHD or corticotherapy ≥ 0.5 mg/kg/day at time of NK cell infusion
  2. Active infection
  3. Psychiatric disorder occurring after transplant
  4. Pregnant or breast-feeding women or without contraception

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NK Cell infusion

  • Cell collection

    o Lymphocytes will be harvest from the original and consenting donor as soon as possible around day 60 post transplantation

  • NK Cell selection

    o Cells will be obtained after double selection: CD3+ depletion followed by CD56+ selection using an european approved device (Miltenyi corporation)

  • NK Cell ex-vivo activation

    o ex-vivo activation: interleukin-2 according to a classical procedure (7 days at 37°C with RPMI clinical grade medium supplemented with 10% of foetal calf serum, 0.5 x 106 cellules / ml, 1000 U/ml d'IL-2 (interleukin, proleukin)

  • NK Cell infusion (60 to 90 days after transplantation)
Biological: NK Cell infusion
  • level 1: 1 x 10e6 NK cells /kg;
  • level 2: 5 x 10e6 NK cells /kg;
  • level 3: > 5.10e6 and ≤ 5.10e7 cellules NK/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurence of grade 3-4 toxicity within 30 days of NK cells infusion
Time Frame: day 30
To establish the safety of donor NK cells infusion after HLA matched allogeneic transplant prepared by RIC.
day 30

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of infused cells population : CD3+, CD56+/CD16+, CD56-/CD16+, CD56+/CD16- (Determination)
Time Frame: baseline: at the time of the NK cells infusion
Ex vivo NK cell selection reproductibility
baseline: at the time of the NK cells infusion
relapse
Time Frame: up to one year after infusion
up to one year after infusion
number of NK cells function form baseline to Month 12 (kinetics)
Time Frame: at Day1, Day2, Day9, Day30, Month3, Month6, Month12

Immunomonitoring: NK ontogeny after in vivo transfer, characterization of KIR expression (phenotype and genotype), documentation of functional activity against tumor cell line and EBV transformed B cell lines. These studies will allow calibrating further the kinetics of NK cells function (cytotoxicity and cytokine production) as well to answer different questions of fundamental immunology

The following studies will be performed:

  1. Analysis of early steps of aGVHD, immune activation and toxicity
  2. Impact of the infusions on NK reconstitution and myeloid cells including dendritic cells
  3. Antileukemic effects
at Day1, Day2, Day9, Day30, Month3, Month6, Month12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Paoli-Calmettes

Investigators

  • Principal Investigator: BLAISE Didier, MD PhD, Institut Paoli-Calmettes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2013

Primary Completion (Actual)

March 15, 2018

Study Completion (Actual)

March 15, 2018

Study Registration Dates

First Submitted

April 4, 2013

First Submitted That Met QC Criteria

May 10, 2013

First Posted (Estimated)

May 15, 2013

Study Record Updates

Last Update Posted (Actual)

April 21, 2026

Last Update Submitted That Met QC Criteria

April 16, 2026

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DLI-NK/IPC 2012-003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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