Childhood Solid TumorPhase 1/2NKNCT01337544
Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours
A Phase 1/2 study testing HAPLOIDENTICAL IL-15 STIMULATED NK CELLS in people with Childhood Solid Tumor, run by Hospital Infantil Universitario Niño Jesús, Madrid, Spain at 1 site in Spain.
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). Read more about this study
- Who is it for?
- Ages 6 months to 22 years
- Conditions the study is for
- Childhood Solid Tumor
- What is being tested?
- HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteSpain
- Study dates
- Jan 2011to Nov 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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%.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Childhood Solid Tumor
- Being tested
- HAPLOIDENTICAL IL-15 STIMULATED NK CELLS
- Keywords
- HAPLOIDENTICAL STEM CELL TRANSPLANTATION, NK CELL, IL-15
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HAPLOIDENTICAL IL-15 STIMULATED NK CELLSOther
Also called CELL THERAPY
ONE MEGADOSE 30 DAYS AFTER TRANSPLANTATION (DOSE WILL DEPEND ON PATIENT BODY WEIGHT)
| Study group | Role | What they receive |
|---|---|---|
| IL-15 STIMULATED NK CELLS | Experimental | Not described Receives: Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events according to NCI-CTC v3.0 CRITERIA as a measure of safety and tolerability
Measured: Up To 1 Year After Transplantation
Secondary outcomes (1)
Objective Response Rate According RECIST V1.1
Measured: Up To One Year After Transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2011 (estimated)
- Study startJan 2011
- Primary completionNov 2012
- Study completionNov 2012
Why it stopped: The parents of two patients enrolled who died, presented a claim against the hospital and the study was halted.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Childhood Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Infantil Universitario Niño Jesús, Madrid, Spain
- Sponsor type
- University, hospital or other
- Collaborators
- SPANISH HEALTH RESEARCH FUND (FIS)
- Responsible party
- Principal investigator, Antonio Perez-Martinez, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
- Investigators
- ANTONIO PEREZ-MARTINEZ, MD, PhD, Principal investigator, HOSPITAL UNIVERSITARIO NINO JESUS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01337544
- Sponsor's protocol ID
- HNJ-NK-01/2009
- Acronym
- NK
- Status last verified
- Nov 2013
- First submitted
- 25 Mar 2011
- Last updated
- 11 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Perez-Martinez A, Leung W, Munoz E, Iyengar R, Ramirez M, Vicario JL, Lassaletta A, Sevilla J, Gonzalez-Vicent M, Madero L, Diaz-Perez 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.
PubMed 19215002
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours
- ClinicalTrials.gov ID
- NCT01337544
- Acronym / sponsor ID
- NK / HNJ-NK-01/2009
- Conditions
- Childhood Solid Tumor
- Keywords
- HAPLOIDENTICAL STEM CELL TRANSPLANTATION, NK CELL, IL-15
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The parents of two patients enrolled who died, presented a claim against the hospital and the study was halted.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Hospital Infantil Universitario Niño Jesús, Madrid, SpainUniversity, hospital or other
- Collaborators
- SPANISH HEALTH RESEARCH FUND (FIS)
- Study start
- Jan 2011
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 19 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IL-15 STIMULATED NK CELLS | Experimental | Other: HAPLOIDENTICAL IL-15 STIMULATED NK CELLS |
Who may qualify
- Ages
- 6 months to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- Serum bilirubin > 3 mg/dl
- GFR < 40 ml/min/1.73 mw
- Cardiac left ventricular ejection fraction < 40%
- HIV+
- Pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HAPLOIDENTICAL IL-15 STIMULATED NK CELLSAlso: CELL THERAPYONE MEGADOSE 30 DAYS AFTER TRANSPLANTATION (DOSE WILL DEPEND ON PATIENT BODY WEIGHT) | Other | IL-15 STIMULATED NK CELLS |
Primary outcome
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
1 secondary outcome
Objective Response Rate According RECIST V1.1
Time frame: Up To One Year After Transplantation
Results and safety
The study was stopped early (reason given: The parents of two patients enrolled who died, presented a claim against the hospital and the study was halted.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2013.
- Background: PubMed 19215002Perez-Martinez A, Leung W, Munoz E, Iyengar R, Ramirez M, Vicario JL, Lassaletta A, Sevilla J, Gonzalez-Vicent M, Madero L, Diaz-Perez 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ANTONIO PEREZ-MARTINEZ, MD, PhD principal investigator
HOSPITAL UNIVERSITARIO NINO JESUS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HAPLOIDENTICAL IL-15 STIMULATED NK CELLS in people with Childhood Solid Tumor, run by Hospital Infantil Universitario Niño Jesús, Madrid, Spain at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The parents of two patients enrolled who died, presented a claim against the hospital and the study was halted.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01337544, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2013.