NeuroblastomaPhase 1STALLONeNCT01460901
Study of Donor Derived, Multi-virus-specific, Cytotoxic T-Lymphocytes for Relapsed/Refractory Neuroblastoma
A Phase 1 study testing GD2 CAR modified Tri-virus specific cytotoxic t-cells in people with Neuroblastoma, run by Children's Mercy Hospital Kansas City at 1 site in United States.
Trial summary
This is a single-center, investigator-initiated, single-arm, pilot study of post-allogeneic transplant, adoptive immunotherapy for the treatment of patients with relapsed/refractory neuroblastoma expressing the mesenchymal tumor marker GD2. Three patients will be treated. Read more about this study
- Who is it for?
- Ages 18 months to 17 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- GD2 CAR modified Tri-virus specific cytotoxic t-cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Jan 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Allogeneic transduced tV-CTLs with >15% expression of 14g2a.zeta chimeric antigen receptor
- Patient or responsible person must be able to understand and sign a permission/assent or consent form for infusion
- Age 18 months through 17 years at time of relapse/progression
- Life expectancy >8weeks
- Karnofsky score 60% or greater if 10 yrs old or older. Lansky score 60% or greater if under 10 yrs old
- Patient must be HIV negative
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- ANC >500
- Pulse ox>90% on room air
- AST/ALT/direct bili <5x upper limit of normal
- Recovered from toxic effects of all prior chemotherapy
- Absence of human/anti-mouse antibody (HAMA) (patients who have received prior therapy with murine antibodies)
- >50% donor engraftment
Who cannot join
- Patient pregnant or lactating or refuses birth control methods
- HIV positive
- Uncontrolled intercurrent infection
- Renal failure (creatinine clearance <40ml/min/1.73m2)
- Active hepatitis or cirrhosis with bilirubin, AST, ALT >5xnormal
- Rapidly progressive disease
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- Currently receiving any investigational drugs
- Tumor potentially causing airway obstruction
- Cardiomegaly or bilateral pulmonary infiltrates on CXR
- Receiving >0.25mg/kg/day methylprednisolone or equivalent systemic steroid. Topical steroid therapy is acceptable
- Receiving more than one lymphocyte inhibiting agent (ex. Tacrolimus/CSA and MMF or other similar agent
- Patients relapsing or progressing before the age of 18 months from Stage I/II disease, and/or those who, in the opinion of their oncologist, may benefit from further conventional therapy
- Donor lymphocyte infusion in last 28 days
- Evidence of GvHD greater than or equal to grade 2
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Mercy Hospital
Kansas City, Missouri, 64108
About this study
Official title: Phase I Study of Donor Derived,Gene Modified, Multi-virus-specific, Cytotoxic T-Lymphocytes Redirected to GD2 for Relapsed/Refractory Neuroblastoma Post-allo Stem Cell Transplantation With Submyeloblative Conditioning
This is a single-center, investigator-initiated, single-arm, pilot study of post-allogeneic transplant, adoptive immunotherapy for the treatment of patients with relapsed/refractory neuroblastoma expressing the mesenchymal tumor marker GD2. Three patients will be treated. The study will focus on the safety and efficacy of allogeneic, donor derived viral specific cytotoxic T-lymphocytes, retrovirally transduced to express a chimeric antigen receptor specific for disialoganglioside, GD2, expressed on neuroblastoma.
Read the detailed description
Neuroblastoma (NB) is the most common extracranial tumor of childhood and prognosis for patients with relapsed or refractory disease is < 10% and there is no standard therapy for these patients. Research toward immunotherapeutic agents has intensified as monoclonal antibody targeting GD2, when incorporated into upfront NB therapy, prolongs survival. Allogeneic Hematopoietic stem cell transplantation (HSCT) has been utilized in patients with NB with evidence of a graft versus tumor (GVT) effect but transplant related mortality (TRM) has nullified the survival benefit. In an effort to harness the GVT effect of allogeneic transplant and lower TRM, harvested viral specific cytotoxic T-cells from the donor will be infused early post-HSCT to the HSCT recipient to shorten the recovery of immunity toward the most significant viral infections. The investigators will also retrovirally transduce the viral specific CTL with a chimeric antigen receptor (CAR) gene complex such that the tV-CTL can expand, via their native T-cell receptors in response to viral infections post-HSCT and carry the capability of killing tumor cells through their transduced receptor which, on the extracellular component of the CAR, has specificity for GD2 expressed on the surface of NB. In essence, the investigators intend to take the specificity of the monoclonal antibody to GD2, already utilized in therapy for NB, and combine this specificity with the cytotoxicity of T-cells to target NB. The investigators hypothesize that the infusion will be safe and viral specificity of the tV-CTL will provide long term immunity to both viral infections and the investigators will see anti-tumor effects.
- Conditions
- Neuroblastoma
- Being tested
- GD2 CAR modified Tri-virus specific cytotoxic t-cells
- Keywords
- Neuroblastoma, Relapsed, Refractory
- Medical subject headings
- Neuroblastoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GD2 CAR modified Tri-virus specific cytotoxic t-cellsBiological
This is a feasibility study to assess safety of an infusion of chimeric-antigen receptor gene modified allogeneic virus specific T lymphocytes after reduced intensity allogeneic stem cell transplant. Three patients were treated and safety was evaluated. Patients received a single infusion of 2x10e6/m2 donor derived, GD2 CAR modified, tri-virus specific CTL performed 30-120 days after allogeneic stem cell transplantation
| Study group | Role | What they receive |
|---|---|---|
| GD2 CAR modified Tri-virus CTL infusion | Experimental | A single infusion of 2x10e6 cells per meter squared was performed 30 to 120 days following allogeneic stem cell transplant. Receives: Biological: GD2 CAR modified Tri-virus specific cytotoxic t-cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Immediate and Short Term Toxicity of Infusion Over 8 Weeks
Immediate: Patients were monitored following infusion to assess for toxicity related to infusion. Potential toxicities related to cellular therapy infusions, such as allergic reaction to the cellular product or cryopreservation media, hemolytic reactions, volume overload, and hemodynamic instability, were monitored.
Short Term: Patients were monitored for 8 weeks for short term toxicity related to infusion. Such adverse reactions monitored were acute graft versus host disease and cytokine release syndrome.
Measured: Post infusion week 8
Peak Transgene Copy Number Per 1000ng PBMC DNA
Peak Transgene Copy Number per 1000ng PBMC DNA from peripheral blood samples measured during study participation.
Measured: 1 year
Death Within 8 Weeks of Infusion
Measured: 8 weeks
Secondary outcomes (2)
Peak Viral Specific SFU/2x10e5 Mononuclear Cells Per Well
The following analyses were performed on peripheral blood samples from patients at protocol assigned time points (pre-infusion, post-infusion at 4 hrs, weeks 1,2,4,6 and 8, month 3, 6 and 12:
ELISPOT assay for CMV, Adenovirus and EBV specific CTL reported as SFU (spot forming unit) per 2x10e5 mononuclear cells
Measured: up to 1 year
Maximum Tumor Response (RECIST 1.1)
Pre and post-therapy evaluation by modalities consistent with prior disease evaluation in each patient. When possible, tumors were assessed per Response Evaluation Criteria In Solid Tumors (RECIST v1.0): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >/=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD) neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Bone marrow aspirations and biopsies were evaluated by histopathology and appropriate immunohistochemistry; Modified Curie score was used for MIBG evaluation.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2011 (estimated)
- Study startOct 2012
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeuroblastomaStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Mercy Hospital Kansas City
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Doug Myers, Children's Mercy Hospital Kansas City
- Investigators
- Doug Myers, MD, Principal investigator, Children's Mercy Hospital Kansas City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01460901
- Sponsor's protocol ID
- STALLONe
- Other IDs
- 00038
- Acronym
- STALLONe
- Status last verified
- Jul 2019
- First submitted
- 25 Oct 2011
- Last updated
- 23 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Donor Derived,Gene Modified, Multi-virus-specific, Cytotoxic T-Lymphocytes Redirected to GD2 for Relapsed/Refractory Neuroblastoma Post-allo Stem Cell Transplantation With Submyeloblative Conditioning
- ClinicalTrials.gov ID
- NCT01460901
- Acronym / sponsor ID
- STALLONe / STALLONe
- Conditions
- Neuroblastoma
- Keywords
- Neuroblastoma, Relapsed, Refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Children's Mercy Hospital Kansas CityUniversity, hospital or other
- Collaborators
- Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Oct 2012
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 27 Oct 2011 (estimated)
- Results
- Posted 23 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-center, investigator-initiated, single-arm, pilot study of post-allogeneic transplant, adoptive immunotherapy for the treatment of patients with relapsed/refractory neuroblastoma expressing the mesenchymal tumor marker GD2. Three patients will be treated. The study will focus on the safety and efficacy of allogeneic, donor derived viral specific cytotoxic T-lymphocytes, retrovirally transduced to express a chimeric antigen receptor specific for disialoganglioside, GD2, expressed on neuroblastoma.
Detailed description
Neuroblastoma (NB) is the most common extracranial tumor of childhood and prognosis for patients with relapsed or refractory disease is < 10% and there is no standard therapy for these patients. Research toward immunotherapeutic agents has intensified as monoclonal antibody targeting GD2, when incorporated into upfront NB therapy, prolongs survival. Allogeneic Hematopoietic stem cell transplantation (HSCT) has been utilized in patients with NB with evidence of a graft versus tumor (GVT) effect but transplant related mortality (TRM) has nullified the survival benefit. In an effort to harness the GVT effect of allogeneic transplant and lower TRM, harvested viral specific cytotoxic T-cells from the donor will be infused early post-HSCT to the HSCT recipient to shorten the recovery of immunity toward the most significant viral infections. The investigators will also retrovirally transduce the viral specific CTL with a chimeric antigen receptor (CAR) gene complex such that the tV-CTL can expand, via their native T-cell receptors in response to viral infections post-HSCT and carry the capability of killing tumor cells through their transduced receptor which, on the extracellular component of the CAR, has specificity for GD2 expressed on the surface of NB. In essence, the investigators intend to take the specificity of the monoclonal antibody to GD2, already utilized in therapy for NB, and combine this specificity with the cytotoxicity of T-cells to target NB. The investigators hypothesize that the infusion will be safe and viral specificity of the tV-CTL will provide long term immunity to both viral infections and the investigators will see anti-tumor effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GD2 CAR modified Tri-virus CTL infusion | Experimental | Biological: GD2 CAR modified Tri-virus specific cytotoxic t-cellsA single infusion of 2x10e6 cells per meter squared was performed 30 to 120 days following allogeneic stem cell transplant. |
Who may qualify
- Ages
- 18 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- Allogeneic transduced tV-CTLs with >15% expression of 14g2a.zeta chimeric antigen receptor
- Patient or responsible person must be able to understand and sign a permission/assent or consent form for infusion
- Age 18 months through 17 years at time of relapse/progression
- Life expectancy >8weeks
- Karnofsky score 60% or greater if 10 yrs old or older. Lansky score 60% or greater if under 10 yrs old
Key exclusion criteria (14 listed)
- Patient pregnant or lactating or refuses birth control methods
- HIV positive
- Uncontrolled intercurrent infection
- Renal failure (creatinine clearance <40ml/min/1.73m2)
- Active hepatitis or cirrhosis with bilirubin, AST, ALT >5xnormal
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 |
|---|---|---|
| GD2 CAR modified Tri-virus specific cytotoxic t-cellsThis is a feasibility study to assess safety of an infusion of chimeric-antigen receptor gene modified allogeneic virus specific T lymphocytes after reduced intensity allogeneic stem cell transplant. Three patients were treated and safety was evaluated. Patients received a single infusion of 2x10e6/m2 donor derived, GD2 CAR modified, tri-virus specific CTL performed 30-120 days after allogeneic stem cell transplantation | Biological | GD2 CAR modified Tri-virus CTL infusion |
Primary outcome
Number of Participants With Immediate and Short Term Toxicity of Infusion Over 8 Weeks
Time frame: Post infusion week 8
Immediate: Patients were monitored following infusion to assess for toxicity related to infusion. Potential toxicities related to cellular therapy infusions, such as allergic reaction to the cellular product or cryopreservation media, hemolytic reactions, volume overload, and hemodynamic instability, were monitored. Short Term: Patients were monitored for 8 weeks for short term toxicity related to infusion. Such adverse reactions monitored were acute graft versus host disease and cytokine release syndrome.
Peak Transgene Copy Number Per 1000ng PBMC DNA
Time frame: 1 year
Peak Transgene Copy Number per 1000ng PBMC DNA from peripheral blood samples measured during study participation.
Death Within 8 Weeks of Infusion
Time frame: 8 weeks
2 secondary outcomes
Peak Viral Specific SFU/2x10e5 Mononuclear Cells Per Well
Time frame: up to 1 year
Maximum Tumor Response (RECIST 1.1)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Children's Mercy Hospitals and ClinicsLink provided by the sponsor.
Related trials for Neuroblastoma
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PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy
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Active, not recruitingPhase 1
GD2 Specific CAR and Interleukin-15 Expressing Autologous NKT Cells to Treat Children With Neuroblastoma
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Not yet recruitingPhase 1
GD2IL18CART Combined With Bevacizumab for Relapsed and Refractory GD2-positive Solid Tumors
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RecruitingPhase 2/3
A Safety and Efficacy Study of hu14 in High-Risk Neuroblastoma Patients
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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.
Doug Myers, MD principal investigator
Children's Mercy Hospital Kansas City
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GD2 CAR modified Tri-virus specific cytotoxic t-cells in people with Neuroblastoma, run by Children's Mercy Hospital Kansas City at 1 site in United States.
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 12 inclusion and 14 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: finished, as of the sponsor's last update on 23 Jul 2019. 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 United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Participants With Immediate and Short Term Toxicity of Infusion Over 8 Weeks (time frame: Post infusion week 8). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jul 2019.