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

Childhood Solid Tumor Clinical Trial

— NK  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01337544
• Other study ID #: HNJ-NK-01/2009
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: March 25, 2011
• Last updated: November 8, 2013
• Start date: January 2011
• Est. completion date: November 2012

Study information

• Verified date: November 2013
• Source: Hospital Infantil Universitario Niño Jesús, Madrid, Spain
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 22 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Childhood Solid Tumor

Intervention

Other:
• HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
ONE MEGADOSE 30 DAYS AFTER TRANSPLANTATION (DOSE WILL DEPEND ON PATIENT BODY WEIGHT)

Locations

Country	Name	City	State
Spain	Hospital Infantil Universitario Niño Jesus	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Infantil Universitario Niño Jesús, Madrid, Spain	SPANISH HEALTH RESEARCH FUND (FIS)

Country where clinical trial is conducted

Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Objective Response Rate According RECIST V1.1		Up To One Year After Transplantation	No

External Links

•   HOSPITAL INFANTIL UNIVERSITARIO NIÑO JESUS