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

NCT01853358 | Completed Phase 1 DMC

• 1 other identifier: DLI-NK/IPC 2012-003
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hematological Malignancy

Keywords

hematological malignancy; stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• Occurence of grade 3-4 toxicity within 30 days of NK cells infusion

  To establish the safety of donor NK cells infusion after HLA matched allogeneic transplant prepared by RIC.

  day 30

Secondary Outcomes (3)

• Number of infused cells population : CD3+, CD56+/CD16+, CD56-/CD16+, CD56+/CD16- (Determination)

  baseline: at the time of the NK cells infusion

• relapse

  up to one year after infusion

• number of NK cells function form baseline to Month 12 (kinetics)

  at Day1, Day2, Day9, Day30, Month3, Month6, Month12

Study Arms (1)

NK Cell infusion

EXPERIMENTAL

* 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

Interventions

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

NK Cell infusion

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead

Study Sites (1)

Institut Paoli-Calmettes

Marseille, 13009, France

Location

Related Publications (2)

• Devillier R, Calmels B, Guia S, Taha M, Fauriat C, Mfarrej B, Venton G, Vivier E, Olive D, Chabannon C, Blaise D, Ugolini S. Phase I Trial of Prophylactic Donor-Derived IL-2-Activated NK Cell Infusion after Allogeneic Hematopoietic Stem Cell Transplantation from a Matched Sibling Donor. Cancers (Basel). 2021 May 28;13(11):2673. doi: 10.3390/cancers13112673.

  PMID: 34071607 RESULT

• Mfarrej B, Gaude J, Couquiaud J, Calmels B, Chabannon C, Lemarie C. Validation of a flow cytometry-based method to quantify viable lymphocyte subtypes in fresh and cryopreserved hematopoietic cellular products. Cytotherapy. 2021 Jan;23(1):77-87. doi: 10.1016/j.jcyt.2020.06.005. Epub 2020 Jul 25.

  PMID: 32718876 RESULT

Related Links

• official web site of the sponsor

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• BLAISE Didier, MD PhD

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2013
• First Posted: May 15, 2013
• Study Start: April 1, 2013
• Primary Completion: March 15, 2018
• Study Completion: March 15, 2018
• Last Updated: April 21, 2026

Record last verified: 2018-07

Locations

FR (1)