Hematological MalignancyPhase 1DLI-NKNCT01853358
Phase I of Infusion of Selected Donor NK Cells After Allogeneic Stem Cell Transplantation
A Phase 1 study testing NK Cell infusion in people with Hematological Malignancy, run by Institut Paoli-Calmettes at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hematological Malignancy
- What is being tested?
- NK Cell infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2013to 15 Mar 2018
- Phase
- Phase 1
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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.
Read the 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.
- Conditions
- Hematological Malignancy
- Being tested
- NK Cell infusion
- Keywords
- hematological malignancy, stem cell transplantation
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NK Cell infusionBiological
- 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
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Biological: NK Cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: day 30
Secondary outcomes (3)
Number of infused cells population : CD3+, CD56+/CD16+, CD56-/CD16+, CD56+/CD16- (Determination)
Ex vivo NK cell selection reproductibility
Measured: baseline: at the time of the NK cells infusion
relapse
Measured: up to one year after infusion
number of NK cells function form baseline to Month 12 (kinetics)
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
Measured: at Day1, Day2, Day9, Day30, Month3, Month6, Month12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2013 (estimated)
- Study startApr 2013
- Primary completion15 Mar 2018
- Study completion15 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hematological MalignancyStudies of the same condition, open and under way.
- More trials run by Institut Paoli-CalmettesThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Paoli-Calmettes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- BLAISE Didier, MD PhD, Principal investigator, Institut Paoli-Calmettes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01853358
- Sponsor's protocol ID
- DLI-NK/IPC 2012-003
- Acronym
- DLI-NK
- Status last verified
- Jul 2018
- First submitted
- 4 Apr 2013
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 34071607Mfarrej 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.
PubMed 32718876
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01853358
- Acronym / sponsor ID
- DLI-NK / DLI-NK/IPC 2012-003
- Conditions
- Hematological Malignancy
- Keywords
- hematological malignancy, stem cell transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (estimated)
- Lead sponsor
- Institut Paoli-CalmettesUniversity, hospital or other
- Study start
- Apr 2013 (actual)
- Primary completion
- 15 Mar 2018 (actual)
- Study completion
- 15 Mar 2018 (actual)
- First posted
- 15 May 2013 (estimated)
- 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.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NK Cell infusion | Experimental | Biological: 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) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patient treated with allogeneic stem cell transplantation
- 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
Key exclusion criteria (4 listed)
- 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
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 |
|---|---|---|
| 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 | Biological | NK Cell infusion |
Primary outcome
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.
3 secondary outcomes
Number of infused cells population : CD3+, CD56+/CD16+, CD56-/CD16+, CD56+/CD16- (Determination)
Time frame: baseline: at the time of the NK cells infusion
relapse
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Results publication: PubMed 34071607Devillier 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.
- Results publication: PubMed 32718876Mfarrej 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.
- official web site of the sponsorLink provided by the sponsor.
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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.
BLAISE Didier, MD PhD principal investigator
Institut Paoli-Calmettes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NK Cell infusion in people with Hematological Malignancy, run by Institut Paoli-Calmettes at 1 site in France.
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 10 inclusion and 4 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: finished, as of the sponsor's last update on 21 Apr 2026. 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 France. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurence of grade 3-4 toxicity within 30 days of NK cells infusion (time frame: day 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01853358, which also lists 2 linked publications.
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 21 Apr 2026.