Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Childhood Solid Tumor |
Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours |
- Number of patients with adverse events according to NCI-CTC v3.0 CRITERIA as a measure of safety and tolerability [ Time Frame: Up To 1 Year After Transplantation ] [ Designated as safety issue: Yes ]
- Objective Response Rate According RECIST V1.1 [ Time Frame: Up To One Year After Transplantation ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 15 |
| Study Start Date: | January 2011 |
| Estimated Study Completion Date: | January 2014 |
| Estimated Primary Completion Date: | January 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: IL-15 STIMULATED NK CELLS |
Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
ONE MEGADOSE 30 DAYS AFTER TRANSPLANTATION (DOSE WILL DEPEND ON PATIENT BODY WEIGHT)
Other Name: CELL THERAPY
|
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| Ages Eligible for Study: | 6 Months to 22 Years |
| Genders Eligible for Study: | Both |
| Accepts 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.
Contacts and Locations| Spain | |
| Hospital Infantil Universitario Niño Jesus | Recruiting |
| Madrid, Spain, 28009 | |
| Contact: ANTONIO PEREZ-MARTINEZ, MD, PhD +34915035938 aperezm.hnjs@salud.madrid.org | |
| Contact: MIGUEL ANGEL DIAZ, MD, PhD +34915035938 mdiaz.hnjs@salud.madrid.org | |
| Principal Investigator: ANTONIO PEREZ-MARTINEZ, MD,PhD | |
| Principal Investigator: | ANTONIO PEREZ-MARTINEZ, MD, PhD | HOSPITAL UNIVERSITARIO NINO JESUS |
More Information
Additional Information:
Publications:
| Responsible Party: | Dr. Antonio Perez Martinez, Hospital Infantil Universitario Nino Jesus |
| ClinicalTrials.gov Identifier: | NCT01337544 History of Changes |
| Other Study ID Numbers: | HNJ-NK-01/2009 |
| Study First Received: | March 25, 2011 |
| Last Updated: | April 18, 2011 |
| Health Authority: | Spain: Spanish Agency of Medicines |
Keywords provided by Hospital Infantil Universitario Niño Jesús, Madrid, Spain:
|
HAPLOIDENTICAL STEM CELL TRANSPLANTATION NK CELL IL-15 |
Additional relevant MeSH terms:
|
Neoplasms |
ClinicalTrials.gov processed this record on June 18, 2013