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Acute Myeloid LeukemiaPhase 1/2NKNCT01947322

Haploidentical NK-cell Infusion in Acute Myeloid Leukemia

A Phase 1/2 study testing Allogenic NK cells infusion in people with Acute Myeloid Leukemia, run by Assistance Publique - Hôpitaux de Paris at 4 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Leukemia cells can be killed by natural killer (NK) from HLA-I mismatched donor. The proposed study plans to realize an adoptive anti-leukaemic immunotherapy by infusion of HLA-I mismatched NK cells to treat poor prognosis acute myeloid leukemia patients. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Allogenic NK cells infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
4 sitesFrance
Study dates
May 2011to Jan 2016
Phase
Phase 1/2
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult
  1. Recipient selection
  2. Patient eligibility
  • Poor prognosis de novo AML including :
  1. Primary refractory disease (absence of complete remission (CR) after at least 2 different induction regimens)
  2. Relapsed disease that did not reach CR after at least 1 salvage therapy
  3. First untreated early relapse (less than one year of remission duration) in the absence of allogeneic HSCT project.
  • Age between 18 and 65
  • No liver and renal dysfunctions contraindicating the administration of Fludarabine, Cyclophosphamide or Cytarabine.
  • Written informed consent
  1. Patient exclusion criteria
  • Secondary AML.
  • Previous autologous or allogeneic transplantation. Since the main objective of the study concerns the hematological toxicity, we decided to exclude patients with secondary AML or who had been previously transplanted because of their expected higher hematological toxicity.
  • Patient with allogeneic transplant project
  • HIV positive serology
  1. Donor eligibility
  • HLA haploidentical brother, sister, child (older than 18 years), father, sister, cousin, uncle, aunt.
  • Donor with KIR ligand mismatch in the GvL direction
  • Absence of contraindication for leukapheresis.
  • Negative HIV1-2, HTLV-1-2, HBV, and HCV serology. Negative viral genomic screening for HTLV1-2 and HCV
  • Written informed consent

Trial locations and contacts

4 sites in 1 country.

France4 sites

  • Service d'Hématologie Clinique du Pr. Leblond- Hôpital Pitié salpêtrière

    Paris, 75013

  • Service d'Hématologie adultes du Pr. Hermine - Hôpital Necker Enfants Malades

    Paris, 75015

  • Service d'Hématologie oncologie du Pr. Mohty -Hôpital Saint Antoine

    Paris, 75571

  • Service d'Hématologie Clinique du Pr. Cordonnier-Hôpital Henri Mondor

    Paris, 94010

Other trials in France

About this study

Official title: Haploidentical NK-cell Infusion in Bad Prognosis AML Patients: Evaluation of Feasibility and Antitumoral Effect

Leukemia cells can be killed by natural killer (NK) from HLA-I mismatched donor. The proposed study plans to realize an adoptive anti-leukaemic immunotherapy by infusion of HLA-I mismatched NK cells to treat poor prognosis acute myeloid leukemia patients. NK cells will be selected from HLA mismatch familial donor peripheral mononuclear cells by purification protocol. Before NK-infusion, patients received immunosuppressive chemotherapy.

Read the detailed description

NK cell-mediated cytotoxity is regulated by signals provided by surface inhibitory and activating receptors. Target cells will be killed in the absence of interaction between NK inhibitory receptors and their ligands (HLA class I molecules) on the target cells. The proposed phase I/II study plans to realize an adoptive anti-leukaemic immunotherapy by infusion of haploidentical HLA-I mismatched NK cells to treat poor prognosis AML patients. Familial donors of NK cells will be selected according to their HLA typing in order to choose a donor with NK cells expressing at least one inhibitory receptor that can not recognize any HLA class I molecule on recipient cells. NK cells will be selected from donor peripheral mononuclear cells by a two step purification protocol (CD3 negative with subsequent CD56 positive selections). NK cells will be then activated ex vivo overnight in the presence of IL-2 before infusion. In vivo IL-2 injections will be performed for 14 days. Before NK-infusion, patients will be conditioned by a cytoreductive and immunosuppressive chemotherapy. An extensive biological study of NK cells will be performed in the recipient post-infusion, including chimerism analyses, phenotypic and functional tests in order to evaluate NK-cell expansion post-infusion and their capacity to mediate an antitumoral effect. Since donor NK cells have been selected for their potential graft versus host (GvH) and graft versus leukemia (GvL) reactivity, such approach might induce prolonged cytopenia due to a direct toxicity of NK cells against normal hematopoietic progenitors. The main goals of this study will be thus to evaluate (1) the hematological feasibility of allogeneic NK-cell infusion, (2) the expansion of the infused population, (3) an antitumoral effect mediated by this adoptive immunotherapy. This is an essential step before further development of such anti-tumoral immunotherapeutic approach, in leukemic patients but also in solid tumors that could be sensitive to an "NK-effect" (melanoma, kidney cancer).

This project includes 4 clinical departments and several laboratories of cellular therapy and immunology that have got an expertise in the field of Acute Myeloid Leukemia (AML), cellular therapy and NK-cell.

Being tested
Allogenic NK cells infusion
Keywords
Natural killer cell, Haploidentical, Acute myeloid leukemia, Chemotherapy
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogenic NK cells infusionDrug

    Also called cellular therapy

    HLA Haploidentical selected NK cell infusion (one injection of 1x107/kg CD3-CD56+ cells) after chemotherapy associating fludarabine, cytosine arabinoside and cyclophosphamide.

Study groups in NCT01947322
Study groupRoleWhat they receive
Allogenic NK cells infusionExperimentalNot described
Receives: Drug: Allogenic NK cells infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. duration of neutropenia inferior to 500 neutrophils /mm3

    Measured: from the day of NK infusion (day 0) up to 35 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2013 (estimated)
  2. Study startMay 2011
  3. Primary completionJan 2016
  4. Study completionJan 2016

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01947322
Sponsor's protocol ID
P070505
Acronym
NK
Status last verified
Aug 2017
First submitted
26 Mar 2013
Last updated
29 Aug 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Allogenic NK cells infusion in people with Acute Myeloid Leukemia, run by Assistance Publique - Hôpitaux de Paris at 4 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 29 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

duration of neutropenia inferior to 500 neutrophils /mm3 (time frame: from the day of NK infusion (day 0) up to 35 days). 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 NCT01947322.

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 29 Aug 2017.

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