Clinical trial NCT01337544: Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours
Official title: Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Childhood Solid Tumor
Keywords: HAPLOIDENTICAL STEM CELL TRANSPLANTATION
NK CELL
IL-15
Lead sponsor: Hospital Infantil Universitario Niño Jesús, Madrid, Spain
Sponsor class: OTHER
Collaborators: name: SPANISH HEALTH RESEARCH FUND (FIS)
First posted: 2011-04-19
Enrollment: 6
Sex: ALL
Minimum age (years): 6
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients with adverse events according to NCI-CTC v3.0 CRITERIA as a measure of safety and tolerability
timeFrame: Up To 1 Year After Transplantation
Secondary outcomes:
measure: Objective Response Rate According RECIST V1.1
timeFrame: Up To One Year After Transplantation
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesus
Study officials:
affiliation: HOSPITAL UNIVERSITARIO NINO JESUS
name: ANTONIO PEREZ-MARTINEZ, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perez-Martinez A, Leung W, Munoz E, Iyengar R, Ramirez M, Vicario JL, Lassaletta A, Sevilla J, Gonzalez-Vicent M, Madero L, Diaz-Perez 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.