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

Conditions

Childhood Solid Tumor

Keywords

HAPLOIDENTICAL STEM CELL TRANSPLANTATION, NK CELL, IL-15

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.

Related papers

No related papers found yet.

Interventions

OTHERHAPLOIDENTICAL IL-15 STIMULATED NK CELLS

ONE MEGADOSE 30 DAYS AFTER TRANSPLANTATION (DOSE WILL DEPEND ON PATIENT BODY WEIGHT)

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Months to 22 Years

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.

Design outcomes

Primary

Measure	Time frame
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

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

Countries

Spain

Outcome results

None listed