Refractory NeuroblastomaPhase 1PHOX2BNCT07007117
PHOX2B PC-CAR T Cells for Relapsed Neuroblastoma
A Phase 1 study testing PHOX2B PC-CAR T Cells in people with Refractory Neuroblastoma and Relapsed Neuroblastoma, run by Stephan Grupp MD PhD at 1 site in United States.
Trial summary
This is a first in human dose escalation trial to determine the safety of administering PHOX2B PC-CAR T cells in patients with advanced, high-risk neuroblastoma. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Refractory Neuroblastoma, Relapsed Neuroblastoma, High-Risk Neuroblastoma
- What is being tested?
- PHOX2B PC-CAR T Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2025to 30 Jun 2035
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must be ≥ 1 years of age
- Patients must demonstrate expression of at least one of the following HLA alleles by HLA genotyping (conducted at CHOP) to be eligible:
- HLA-A24:02, HLA-A24:03, HLA-A24:04, HLA-A24:07, HLA-A24:124, HLA-A24:143, HLA-A24:17, HLA-A24:242, HLA-A24:305, HLA-A24:314, HLA-A24:33, HLA-A24:353, HLA-A24:41, HLA-A24:51, HLA-A24:63, HLA-A24:87, HLA-A24:92, HLA-A23:01, HLA-A23:17, HLA-A23:25, HLA-A23:39,
- Disease Status A. Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low- or intermediate-risk, but then reclassified as high-risk are also eligible.
- Patients must have a previously histologically confirmed diagnosis of neuroblastoma.
- Patients must have recurrent/progressive, refractory or persistent neuroblastoma.
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- Patients must have neuroblastoma for which standard curative measures do not exist or are no longer effective. Note: Patients at first relapse are eligible as no known curative therapies exist for relapsed high-risk neuroblastoma.
- Patients must have evaluable or measurable disease at enrollment and at least one of the following:
- Bone Sites
- MIBG avid tumors:
- Patients with recurrent/progressive or refractory disease:
- At least 1 MIBG avid bone site.
- Patients with persistent disease:
- 3 or more MIBG avid sites (including soft tissue and/or bone).
- 1 or 2 MIBG avid sites (including soft tissue and/or bone) with biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment.
- MIBG non-avid tumors: at least 1 bone lesion with either biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment OR both FDG-PET uptake AND MRI consistent with metastasis.
- Bone marrow: Any amount of tumor cells in the bone marrow (including neuroblasts, mature and maturing ganglion cells).
- Soft tissue site(s) a) At least one soft tissue lesion that meets criteria for a target lesion as defined by: 1. Size: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm or for discrete lymph nodes ≥ 15 mm short axis.
- 2. In addition to size, a lesion needs to meet ONE of the following criteria:
- MIBG avid tumors: i. Patients with recurrent/progressive or refractory disease:
- 1. At least one MIBG avid soft tissue site. ii. Patients with persistent disease:
- 3 or more MIBG avid sites (including soft tissue and/or bone).
- 1 or 2 MIBG avid sites (including soft tissue and/or bone), with biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment.
- MIBG non-avid tumors: biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma (with or without FDG uptake) in a soft tissue site present at time of enrollment OR both FDG-PET uptake AND MRI consistent with metastasis.
- At least one soft tissue lesion that does not meet size criteria for a target lesion but had a biopsy positive for neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment OR is in a patient with recurrent/progressive or refractory disease and is MIBG avid.
- 4. Patients must have a Lansky (≤ 16 years) or Karnofsky (> 16 years) score of ≥ 60.
- 5. Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age.
- 6. Liver Function as follows:
- Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease or liver metastases).
- Alanine aminotransferase (ALT) ≤ 3.0 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).
- Aspartate aminotransferase (AST) ≤ 3.0 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).
- 7. Pulmonary Function as follows:
- Patients need to have a baseline pulse oximetry of at least 92% on room air and DLCO ≥ 60% (corrected for anemia if necessary) if PFTs are clinically appropriate as determined by the treating investigator.
- 8. Cardiac Function as follows:
- Left ventricular shortening fraction (LVSF) ≥28% or ejection fraction (LVEF) ≥ 50% confirmed by Echo, or adequate ventricular function documented by a scan or a cardiologist.
- 9. Patients of child-bearing potential ( patients who have reached menarche and have not experienced treatment-related premature ovarian failure) must have a negative serum pregnancy test performed at the time of screening It is recommended that all patients of reproductive potential use at least one medically acceptable form of contraception for at least 1 year after their last infusion of PHOX2B PC-CAR T cells. Investigators shall counsel patients on the importance of pregnancy prevention and the implications of an unexpected pregnancy.
Who cannot join
- Patients with active hepatitis B or active hepatitis C.
- Patients with active HIV infection (patients undergoing anti-retroviral therapy with undetectable HIV viral load are eligible).
- Patients with uncontrolled active infection.
- Patients with primary or acquired immunodeficiency disorder.
- Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
- Patients with actively progressing CNS metastases, including parenchymal or leptomeningeal involvement. (Note: CNS imaging at screening is only required if there is a clinical indication of suspected CNS metastasis)
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- Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and/or neurotoxicity.
- Patients who have received any live vaccines within 30 days prior to enrollment.
- Pregnant or nursing (lactating) patients.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 1 Trial of PHOX2B Peptide-Centric Chimeric Antigen Receptor Autologous T Cells (PHOX2B PC-CAR T) for Relapsed Neuroblastoma
This is a first in human dose escalation trial to determine the safety of administering PHOX2B PC-CAR T cells in patients with advanced, high-risk neuroblastoma.
Read the detailed description
Neuroblastoma is a tumor of childhood arising from neural crest-derived cells of the developing sympathetic nervous system. While neuroblastomas in young infants often spontaneously regress, children diagnosed with advanced disease after 18 months of age experience poor overall survival despite intensive therapy.
Neuroblastoma is a heterogenous disease, but approximately 50% of patients have a "high-risk" clinical phenotype defined by well-established clinical signs and molecular biomarkers. Over 50% of patients ultimately relapse and survivors are often burdened with significant long-term therapy related morbidities. There is no known cure for patients with relapsed high-risk neuroblastoma. PHOX2B as a therapeutic target for neuroblastoma Paired like homeobox 2B (PHOX2B) is a homeodomain transcription factor that promotes differentiation of neural crest cell derived sympathetic nervous system precursor cells. The PHOX2B protein is so specifically expressed in neuroblastoma that it is used an immunohistochemical confirmation of diagnosis. While PHOX2B is expressed during fetal development, PHOX2B expression is silenced in the vast majority of normal tissues after birth.
To therapeutically leverage this differential expression, an HLA restricted PHOX2B PC-CAR T cell was developed and showed potent inhibition of the growth of neuroblastoma patient-derived xenografts. This investigation will be a single institution, open-label first in human, dose escalation and expansion study designed to assess the safety, tolerability, and manufacturing feasibility of PHOX2B- PC CAR T Cells.
- Being tested
- PHOX2B PC-CAR T Cells
- Keywords
- Neuroblastoma, PHOX2B PC-CAR T Cells, Cell Therapy
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PHOX2B PC-CAR T CellsBiological
The PHOX2B PC-CAR T cell investigational product is comprised of autologous human T cells that have been genetically modified to express a a PHOX2B-targeting chimeric antigen receptor (CAR) transgene.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | The dose escalation arm will determine the maximum tolerated dose of PHOX2B PC-CAR T cells using a standard 3+3 trial design. Receives: Biological: PHOX2B PC-CAR T Cells |
| Dose Expansion | Experimental | If at least one dose from the dose expansion arm is determined to be safe, additional patients will be enrolled to the dose expansion arm to preliminarily evaluate the rate of response to PHOX2B-PC CAR T cells and further characterize the safety profile of PHOX2B-PC CAR T Cells Receives: Biological: PHOX2B PC-CAR T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the Maximum Tolerated Dose of PHOX2B PC-CAR T Cells
The Maximum Tolerated Dose of PHOX2B-PC CAR T cells will be determined by measuring the incidence of dose limiting toxicities following administration of the product.
Measured: 5 years
Frequency of Adverse Events Following PHOX2B PC-CAR T cell administration
Assess the frequency and severity of treatment related adverse events following administration of PHOX2B PC-CAR T cells.
Measured: 5 years
Secondary outcomes (4)
Manufacturing Feasibility of PHOX2B PC-CAR T cells
Manufacturing Feasibility will be evaluated as the Percentage of patients with PHOX2B PC- CAR T cell products that meet release criteria
Measured: 5 years
Persistence of PHOX2B PC-CAR T cells
Persistence of PHOX2B PC-CAR T cells will be measured by Polymerase Chain Reaction (or flow cytometry) analysis of whole blood to detect and quantify survival of PHOX2B PC-CAR T cells over time.
Measured: 5 years
Preliminarily define the clinical activity of PHOX2B PC-CAR T cells in patients with relapsed or refractory neuroblastoma
Overall Response Rate will be determined based on international Neuroblastoma Response Criteria
Measured: 5 years
Severity of Adverse Events Following Repeated dosing of PHOX2B PC-CAR T Cells
The safety of PHOX2B PC-CAR T cell therapy reinfusions will be measured by the monitoring the frequency and severity of adverse events after multiple PHOX2B PC-CAR T cells infusions.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2025
- Study start20 Jun 2025
- Primary completion30 Jun 2032 (estimated)
- Study completion30 Jun 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stephan Grupp MD PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Philadelphia, Alliance for Cancer Gene Therapy, Children's Cancer Research Fund
- Responsible party
- Sponsor-investigator, Stephan Grupp MD PhD, Children's Hospital of Philadelphia
- Investigators
- Jacquelyn Crane, MD, Study director, Children's Hospital of PhiladelphiaStephan A. Grupp, MD, PhD, Study director, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07007117
- Sponsor's protocol ID
- 25-023155
- Other IDs
- 25CT012
- Acronym
- PHOX2B
- Status last verified
- Jun 2026
- First submitted
- 28 May 2025
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial of PHOX2B Peptide-Centric Chimeric Antigen Receptor Autologous T Cells (PHOX2B PC-CAR T) for Relapsed Neuroblastoma
- ClinicalTrials.gov ID
- NCT07007117
- Acronym / sponsor ID
- PHOX2B / 25-023155
- Keywords
- Neuroblastoma, PHOX2B PC-CAR T Cells, Cell Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Stephan Grupp MD PhDUniversity, hospital or other
- Collaborators
- Children's Hospital of Philadelphia, Alliance for Cancer Gene Therapy, Children's Cancer Research Fund
- Study start
- 20 Jun 2025 (actual)
- Primary completion
- 30 Jun 2032 (estimated)
- Study completion
- 30 Jun 2035 (estimated)
- First posted
- 5 Jun 2025 (actual)
- 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.
This is a first in human dose escalation trial to determine the safety of administering PHOX2B PC-CAR T cells in patients with advanced, high-risk neuroblastoma.
Detailed description
Neuroblastoma is a tumor of childhood arising from neural crest-derived cells of the developing sympathetic nervous system. While neuroblastomas in young infants often spontaneously regress, children diagnosed with advanced disease after 18 months of age experience poor overall survival despite intensive therapy.
Neuroblastoma is a heterogenous disease, but approximately 50% of patients have a "high-risk" clinical phenotype defined by well-established clinical signs and molecular biomarkers. Over 50% of patients ultimately relapse and survivors are often burdened with significant long-term therapy related morbidities. There is no known cure for patients with relapsed high-risk neuroblastoma. PHOX2B as a therapeutic target for neuroblastoma Paired like homeobox 2B (PHOX2B) is a homeodomain transcription factor that promotes differentiation of neural crest cell derived sympathetic nervous system precursor cells. The PHOX2B protein is so specifically expressed in neuroblastoma that it is used an immunohistochemical confirmation of diagnosis. While PHOX2B is expressed during fetal development, PHOX2B expression is silenced in the vast majority of normal tissues after birth.
To therapeutically leverage this differential expression, an HLA restricted PHOX2B PC-CAR T cell was developed and showed potent inhibition of the growth of neuroblastoma patient-derived xenografts. This investigation will be a single institution, open-label first in human, dose escalation and expansion study designed to assess the safety, tolerability, and manufacturing feasibility of PHOX2B- PC CAR T Cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Biological: PHOX2B PC-CAR T CellsThe dose escalation arm will determine the maximum tolerated dose of PHOX2B PC-CAR T cells using a standard 3+3 trial design. |
| Dose Expansion | Experimental | Biological: PHOX2B PC-CAR T CellsIf at least one dose from the dose expansion arm is determined to be safe, additional patients will be enrolled to the dose expansion arm to preliminarily evaluate the rate of response to PHOX2B-PC CAR T cells and further characterize the safety profile of PHOX2B-PC CAR T Cells |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (36 listed)
- Patients must be ≥ 1 years of age
- Patients must demonstrate expression of at least one of the following HLA alleles by HLA genotyping (conducted at CHOP) to be eligible:
- HLA-A24:02, HLA-A24:03, HLA-A24:04, HLA-A24:07, HLA-A24:124, HLA-A24:143, HLA-A24:17, HLA-A24:242, HLA-A24:305, HLA-A24:314, HLA-A24:33, HLA-A24:353, HLA-A24:41, HLA-A24:51, HLA-A24:63, HLA-A24:87, HLA-A24:92, HLA-A23:01, HLA-A23:17, HLA-A23:25, HLA-A23:39,
- Disease Status A. Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low- or intermediate-risk, but then reclassified as high-risk are also eligible.
- Patients must have a previously histologically confirmed diagnosis of neuroblastoma.
Key exclusion criteria (9 listed)
- Patients with active hepatitis B or active hepatitis C.
- Patients with active HIV infection (patients undergoing anti-retroviral therapy with undetectable HIV viral load are eligible).
- Patients with uncontrolled active infection.
- Patients with primary or acquired immunodeficiency disorder.
- Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
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 |
|---|---|---|
| PHOX2B PC-CAR T CellsThe PHOX2B PC-CAR T cell investigational product is comprised of autologous human T cells that have been genetically modified to express a a PHOX2B-targeting chimeric antigen receptor (CAR) transgene. | Biological | Dose Escalation, Dose Expansion |
Primary outcome
Determine the Maximum Tolerated Dose of PHOX2B PC-CAR T Cells
Time frame: 5 years
The Maximum Tolerated Dose of PHOX2B-PC CAR T cells will be determined by measuring the incidence of dose limiting toxicities following administration of the product.
Frequency of Adverse Events Following PHOX2B PC-CAR T cell administration
Time frame: 5 years
Assess the frequency and severity of treatment related adverse events following administration of PHOX2B PC-CAR T cells.
4 secondary outcomes
Manufacturing Feasibility of PHOX2B PC-CAR T cells
Time frame: 5 years
Persistence of PHOX2B PC-CAR T cells
Time frame: 5 years
Preliminarily define the clinical activity of PHOX2B PC-CAR T cells in patients with relapsed or refractory neuroblastoma
Time frame: 5 years
Severity of Adverse Events Following Repeated dosing of PHOX2B PC-CAR T Cells
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
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Neuroblastoma
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.
Jacquelyn Crane, MD study director
Children's Hospital of Philadelphia
Stephan A. Grupp, MD, PhD study director
Children's Hospital of Philadelphia
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 PHOX2B PC-CAR T Cells in people with Refractory Neuroblastoma and Relapsed Neuroblastoma, run by Stephan Grupp MD PhD 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 36 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 1 Jul 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Determine the Maximum Tolerated Dose of PHOX2B PC-CAR T Cells (time frame: 5 years). The study lists 2 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 1 Jul 2026.