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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Childhood Solid Tumor

Intervention / Treatment
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* Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IL-15 STIMULATED NK CELLS<br> | Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS<br>* ONE MEGADOSE 30 DAYS AFTER TRANSPLANTATION (DOSE WILL DEPEND ON PATIENT BODY WEIGHT)<br>* Other names: CELL THERAPY;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAPLOIDENTICAL STEM CELL TRANSPLANTATION, NK CELL, IL-15