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

This study has been terminated.
(The parents of two patients enrolled who died, presented a claim against the hospital and the study was halted.)
Sponsor:
Collaborator:
SPANISH HEALTH RESEARCH FUND (FIS)
Information provided by (Responsible Party):
Antonio Perez-Martinez, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
ClinicalTrials.gov Identifier:
NCT01337544
First received: March 25, 2011
Last updated: November 8, 2013
Last verified: November 2013

March 25, 2011
November 8, 2013
January 2011
November 2012   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01337544 on ClinicalTrials.gov Archive Site
Objective Response Rate According RECIST V1.1 [ Time Frame: Up To One Year After Transplantation ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours
Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Childhood Solid Tumor
Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
ONE MEGADOSE 30 DAYS AFTER TRANSPLANTATION (DOSE WILL DEPEND ON PATIENT BODY WEIGHT)
Other Name: CELL THERAPY
Experimental: IL-15 STIMULATED NK CELLS
Intervention: Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
6
November 2012
November 2012   (final data collection date for primary outcome measure)

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.
Both
6 Months to 22 Years
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01337544
HNJ-NK-01/2009
No
Antonio Perez-Martinez, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Hospital Infantil Universitario Niño Jesús, Madrid, Spain
SPANISH HEALTH RESEARCH FUND (FIS)
Principal Investigator: ANTONIO PEREZ-MARTINEZ, MD, PhD HOSPITAL UNIVERSITARIO NINO JESUS
Hospital Infantil Universitario Niño Jesús, Madrid, Spain
November 2013

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