PHOX2B PC-CAR T Cells for Relapsed Neuroblastoma

Launched by STEPHAN GRUPP MD PHD · May 28, 2025

Keywords

ClinConnect Summary

This clinical trial, titled "PHOX2B PC-CAR T Cells for Relapsed Neuroblastoma," is exploring a new treatment for children and young adults with high-risk neuroblastoma that has come back after previous treatments or has not responded to standard therapies. The researchers want to find out how safe it is to give a special type of immune cell, known as PHOX2B PC-CAR T cells, to patients with this challenging condition. The trial is currently not recruiting participants, but it aims to include patients aged one year and older who have a confirmed diagnosis of neuroblastoma and specific genetic markers.

To be eligible for the trial, participants must meet several criteria, including showing signs of ongoing disease and having certain health markers. Participants will undergo careful health evaluations and will be monitored closely during the trial. This is a first step in testing this new treatment, so while it may offer hope for managing a difficult-to-treat cancer, it's important to discuss all potential risks and benefits with your healthcare team.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Patients must be ≥ 1 years of age
• • 2. Patients must demonstrate expression of at least one of the following HLA alleles by HLA genotyping (conducted at CHOP) to be eligible.
• • HLA-A\*24:02 HLA-A\*24:03 HLA-A\*24:04 HLA-A\*24:07 HLA-A\*24:124 HLA-A\*24:143 HLA-A\*24:17 HLA-A\*24:242 HLA-A\*24:305 HLA-A\*24:314 HLA-A\*24:33 HLA-A\*24:353 HLA-A\*24:41 HLA-A\*24:51 HLA-A\*24:63 HLA-A\*24:87 HLA-A\*24:92 HLA-A\*23:01 HLA-A\*23:17 HLA-A\*23:25 HLA-A\*23:39
• • 3. 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.
• • 4. Patients must have a previously histologically confirmed diagnosis of neuroblastoma That is recurrent/relapsed or refractory/persistent according to INRC AND For which standard curative measures do not exist or are no longer effective. Patients at first relapse are eligible as no known curative therapies exist for relapsed high-risk neuroblastoma.
• 5. Patients must have evaluable or measurable disease at enrollment. 5. The patient must have experienced at least one of the following:
• • a. New disease site documented on at least one of the following: i. 123I-meta-iodobenzylguanidine (MIBG) or 18F-mFBG (meta-fluorobenzylguanidine) scan; OR ii. CT/MRI; OR iii. FDG or Ga-68 Dotatate PET (in patients known to have MIBG non-avid tumor) and MRI findings consistent with tumor (i.e., bone lesions), OR iv. Biopsy confirmed neuroblastoma for any new or progressing lesion. b. Greater than 20% increase in a least one dimension of soft tissue mass documented by CT/MRI and a minimum absolute increase of 5 mm in longest dimension in existing lesion(s). Previously irradiated lesions may be included.
• • c. Bone marrow biopsy shows progressive disease according to the revised INRC.61 d. Stable persistent disease, such that response at the completion of upfront therapy or salvage therapy is less than partial response AND has a biopsy of at least one site showing viable neuroblastoma.
• • e. Responding persistent disease, defined as at least a partial response to frontline therapy (i.e., at least a partial response to frontline therapy but still has residual disease by MIBG scan, CT/MRI, or bone marrow aspirations/biopsies). Patients in this category are required to have histologic confirmation of viable neuroblastoma from at least one residual site (tumor seen on routine bone marrow morphology is sufficient)
• • 6. Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60.
• • 7. Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age: Age Male Female 12 months to \< 2 years 0.6 0.6 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1.0 1.0 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4
• • 16 years 1.7 1.4
• 8. Liver Function as follows:
• • 1. Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease or liver metastases).
• • 2. Alanine aminotransferase (ALT) ≤ 3.0 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).
• • 3. Aspartate aminotransferase (AST) ≤ 3.0 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases).
• 9. Pulmonary Function as follows:
• • a. Patients need to have a baseline pulse oximetry of at least 92% on room air and DLCO ≥ 60% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator.
• 8. Cardiac Function as follows:
• • a. 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.
• • 10. 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.
• Exclusion Criteria:
• • 1. Patients with active hepatitis B or active hepatitis C. 2. Patients with active HIV infection (patients undergoing anti-retroviral therapy with undetectable HIV viral load are eligible).
• • 3. Patients with uncontrolled active infection 4. Patients with primary or acquired immunodeficiency disorder. 5. 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.
• • 6. 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) 7. Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and/or neurotoxicity.
• • 8. Patients who have received any live vaccines within 30 days prior to enrollment.
• • 9. Pregnant or nursing (lactating) patients.