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

Sponsors

Lead sponsor: Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Collaborator: SPANISH HEALTH RESEARCH FUND (FIS)

Source Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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.

Overall Status Terminated
Start Date January 2011
Completion Date November 2012
Primary Completion Date November 2012
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
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 Outcome
Measure Time Frame
Objective Response Rate According RECIST V1.1 Up To One Year After Transplantation
Enrollment 6
Condition
Intervention

Intervention type: Other

Intervention name: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS

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

Arm group label: IL-15 STIMULATED NK CELLS

Other name: CELL THERAPY

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.

Gender: All

Minimum age: 6 Months

Maximum age: 22 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
ANTONIO PEREZ-MARTINEZ, MD, PhD Principal Investigator HOSPITAL UNIVERSITARIO NINO JESUS
Location
facility Hospital Infantil Universitario Niño Jesus
Location Countries

Spain

Verification Date

November 2013

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Hospital Infantil Universitario Niño Jesús, Madrid, Spain

Investigator full name: Antonio Perez-Martinez

Investigator title: Servicio de Hemato-Oncología Pediátrica

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: IL-15 STIMULATED NK CELLS

Arm group type: Experimental

Acronym NK
Study Design Info

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov