Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01337544
Recruitment Status : Terminated (The parents of two patients enrolled who died, presented a claim against the hospital and the study was halted.)
First Posted : April 19, 2011
Last Update Posted : November 11, 2013
Sponsor:
Collaborator:
SPANISH HEALTH RESEARCH FUND (FIS)
Information provided by (Responsible Party):
Antonio Perez-Martinez, Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Tracking Information
First Submitted Date  ICMJE March 25, 2011
First Posted Date  ICMJE April 19, 2011
Last Update Posted Date November 11, 2013
Study Start Date  ICMJE January 2011
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2011)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2011)
Objective Response Rate According RECIST V1.1 [ Time Frame: Up To One Year After Transplantation ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours
Official Title  ICMJE Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Childhood Solid Tumor
Intervention  ICMJE Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
ONE MEGADOSE 30 DAYS AFTER TRANSPLANTATION (DOSE WILL DEPEND ON PATIENT BODY WEIGHT)
Other Name: CELL THERAPY
Study Arms  ICMJE Experimental: IL-15 STIMULATED NK CELLS
Intervention: Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
Publications * Pérez-Martínez A, Leung W, Muñoz E, Iyengar R, Ramírez M, Vicario JL, Lassaletta A, Sevilla J, González-Vicent M, Madero L, Díaz-Pérez MA. KIR-HLA receptor-ligand mismatch associated with a graft-versus-tumor effect in haploidentical stem cell transplantation for pediatric metastatic solid tumors. Pediatr Blood Cancer. 2009 Jul;53(1):120-4. doi: 10.1002/pbc.21955.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 8, 2013)
6
Original Estimated Enrollment  ICMJE
 (submitted: April 18, 2011)
15
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 22 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01337544
Other Study ID Numbers  ICMJE HNJ-NK-01/2009
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Antonio Perez-Martinez, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Study Sponsor  ICMJE Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Collaborators  ICMJE SPANISH HEALTH RESEARCH FUND (FIS)
Investigators  ICMJE
Principal Investigator: ANTONIO PEREZ-MARTINEZ, MD, PhD HOSPITAL UNIVERSITARIO NINO JESUS
PRS Account Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Verification Date November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP