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NCT Number: NCT01853358

Phase I of Infusion of Selected Donor NK Cells After Allogeneic Stem Cell Transplantation

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.

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Key information

Conditions

Hematological Malignancy Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Neoplasms Neoplasms by Site

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Institut Paoli-Calmettes

Marseille, 13009, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • Age above 18 and under 70
  • Eastern Cooperative Oncology Group (ECOG) 0-1 or Karnofsky index ≥ 70 %
  • Survival expectation > 6 months
  • Affiliation to social security
  • Signed informed consent from Donor and Patient

Exclusion criteria

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

Treatment and study plan

NK cell infusion

Biological
  • 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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. relapse

    Time frame: up to one year after infusion

  3. 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:

    • Analysis of early steps of aGVHD, immune activation and toxicity
    • Impact of the infusions on NK reconstitution and myeloid cells including dendritic cells
    • Antileukemic effects

Sponsors and collaborators

Lead sponsor

Institut Paoli-Calmettes

Other

Registry information

Official study title

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

Acronym: DLI-NK

Important dates

Study start
2013
Primary completion
2018
Study completion
2018
First posted
May 15, 2013
Registry last updated
Apr 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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