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Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours

Sponsor
Hospital Infantil Universitario Niño Jesús, Madrid, Spain (Other)
Overall Status
Terminated
CT.gov ID
NCT01337544
Collaborator
SPANISH HEALTH RESEARCH FUND (FIS) (Other)
6
Enrollment
1
Location
1
Arm
22
Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators propose a new antitumor cell therapy for treating childhood refractory solid tumours. The aim of this study is explore the graft versus tumour effect mediated by allogenic natural killer cells (NKs). NK cell alloreactivity can be predicted by donor killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I alleles mismatch. Cells without an inhibitory HLA ligand may trigger natural killer cell activation and elimination of those target cells. Reduced risk of relapsed has been described in malignant cancer after haploidentical stem cell transplantation when HLA ligands against the inhibitory KIRs present in the donor were absent in the recipient (KIR-HLA receptor-ligand mismatch). NK alloreactivity could also be obtained by Natural Killer Receptor (NCR), Toll-Like-Receptors (TLRs) and NKG2D receptor stimulation mediated by cytokines or tumour cell lines.

This will be an open, non randomized, Phase I/II clinical trial, with a double objective:

therapeutic exploratory. The investigators aim at studying safety and efficacy of haploidentical stem cell transplantation for the treatment of these malignancies with no cure known. Patients will receive an haploidentical stem cell transplantation, followed by IL-15 stimulated NK cells infusion one month after transplantation. Efficacy of the procedure will be evaluated with up-to-date radiological techniques, molecular studies and functional assays.

Condition or Disease Intervention/Treatment Phase
  • Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
 Phase 1/Phase 2

Detailed Description

The investigators propose a new antitumor cell therapy for treating childhood refractory solid tumours. The aim of this study is explore the graft versus tumour effect mediated by allogenic natural killer cells (NKs). NK cell alloreactivity can be predicted by donor killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I alleles mismatch. Cells without an inhibitory HLA ligand may trigger natural killer cell activation and elimination of those target cells. Reduced risk of relapsed has been described in malignant cancer after haploidentical stem cell transplantation when HLA ligands against the inhibitory KIRs present in the donor were absent in the recipient (KIR-HLA receptor-ligand mismatch). NK alloreactivity could also be obtained by Natural Killer Receptor (NCR), Toll-Like-Receptors (TLRs) and NKG2D receptor stimulation mediated by cytokines or tumour cell lines.

Study Design

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours
Study Start Date :
Jan 1, 2011
Actual Primary Completion Date :
Nov 1, 2012
Actual Study Completion Date :
Nov 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: IL-15 STIMULATED NK CELLS

Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
ONE MEGADOSE 30 DAYS AFTER TRANSPLANTATION (DOSE WILL DEPEND ON PATIENT BODY WEIGHT)
Other Names:
  • CELL THERAPY

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of patients with adverse events according to NCI-CTC v3.0 CRITERIA as a measure of safety and tolerability [Up To 1 Year After Transplantation]

    Secondary Outcome Measures

    1. Objective Response Rate According RECIST V1.1 [Up To One Year After Transplantation]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Months to 22 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age 6 months to 22 years.

    • Histological solid tumor confirmation.

    • Measurable solid tumor by image or molecular techniques.

    • Solid tumors that have failed to at least 2 chemotherapy protocols.

    • Suitable haploidentical donor available.

    • Lansky score > 60%.

    Exclusion Criteria:

    • Serum bilirubin > 3 mg/dl

    • GFR < 40 ml/min/1.73 mw

    • Cardiac left ventricular ejection fraction < 40%

    • HIV+

    • Pregnant

    • Unfavorable psycho-social report.

    • Antecedent of abandonment treatment.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hospital Infantil Universitario Niño Jesus Madrid Spain 28009

    Sponsors and Collaborators

    • Hospital Infantil Universitario Niño Jesús, Madrid, Spain
    • SPANISH HEALTH RESEARCH FUND (FIS)

    Investigators

    • Principal Investigator: ANTONIO PEREZ-MARTINEZ, MD, PhD, HOSPITAL UNIVERSITARIO NINO JESUS

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Antonio Perez-Martinez, Servicio de Hemato-Oncología Pediátrica, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
    ClinicalTrials.gov Identifier:
    NCT01337544
    Other Study ID Numbers:
    • HNJ-NK-01/2009
    First Posted:
    Apr 19, 2011
    Last Update Posted:
    Nov 11, 2013
    Last Verified:
    Nov 1, 2013
    Keywords provided by Antonio Perez-Martinez, Servicio de Hemato-Oncología Pediátrica, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
    HAPLOIDENTICAL STEM CELL TRANSPLANTATION
    NK CELL
    IL-15
    Additional relevant MeSH terms:
    Neoplasms

    Study Results

    No Results Posted as of Nov 11, 2013