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

November 8, 2013 updated by: Antonio Perez-Martinez, Hospital Infantil Universitario Niño Jesús, Madrid, Spain

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28009
        • Hospital Infantil Universitario Nino Jesus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 22 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of patients with adverse events according to NCI-CTC v3.0 CRITERIA as a measure of safety and tolerability
Time Frame: Up To 1 Year After Transplantation
Up To 1 Year After Transplantation

Secondary Outcome Measures

Outcome Measure
Time Frame
Objective Response Rate According RECIST V1.1
Time Frame: Up To One Year After Transplantation
Up To One Year After Transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Collaborators

SPANISH HEALTH RESEARCH FUND (FIS)

Investigators

  • Principal Investigator: ANTONIO PEREZ-MARTINEZ, MD, PhD, Hospital Universitario Niño Jesus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (ACTUAL)

November 1, 2012

Study Completion (ACTUAL)

November 1, 2012

Study Registration Dates

First Submitted

March 25, 2011

First Submitted That Met QC Criteria

April 18, 2011

First Posted (ESTIMATE)

April 19, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

November 11, 2013

Last Update Submitted That Met QC Criteria

November 8, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HNJ-NK-01/2009

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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