NeuroblastomaPhase 1NCT06500819
Autologous B7-H3 Chimeric Antigen Receptor T Cells in Relapsed/Refractory Solid Tumors
A Phase 1 study testing B7-H3CART Dose (Intravenous) in people with Neuroblastoma and Sarcoma, run by Stanford University at 1 site in United States.
Trial summary
The purpose of this study is to test the manufacturing feasibility and safety of intravenous (IV) administration of B7-H3CART in children and young adult subjects with relapsed and/or refractory solid tumors expressing B7-H3 target using a standard 3+3 dose escalation design. Read more about this study
- Who is it for?
- Ages 2 to 30 years
- Conditions the study is for
- Neuroblastoma, Sarcoma, Osteosarcoma
- What is being tested?
- B7-H3CART Dose (Intravenous)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jul 2024to Jul 2029
- 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 2 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically confirmed malignant solid tumor (including neuroblastoma, soft tissue sarcoma, osteosarcoma, Ewing Sarcoma, and Wilms tumor) with evidence of incurable disease and tumor recurrence/progression after all available curative standard therapies.
- Subjects with neuroblastoma must have received or be intolerant to anti-GD2 antibody therapy.
- Subjects with Wilm's tumor must have received or be intolerant to ifosfamide or cyclophosphamide plus etoposide therapy or alternative salvage regimen.
- Subjects with embryonal rhabdomyosarcoma must have received or be intolerant to Adriamycin-based therapy.
- Subjects with surgically resected pulmonary osteosarcoma in first recurrence must have received surgical resection of metastatic nodules.
- Subjects during dose escalation must have evaluable or measurable disease. Subjects during dose expansion must have measurable disease, except neuroblastoma which may have MIBG positive disease only.
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- B7-H3 positive expression on malignant cells is NOT required but archival tissue must be available, or the subject must be willing to undergo tissue biopsy for expression analysis.
- Age: Must be ≥ 2 and ≤ 30 years of age.
- For the first three subjects treated with B7-H3CART, must be ≥ 12 and ≤ 30 years of age.
- Performance Status: Patients > 16 years of age must have Karnofsky ≥ 50%. Patients ≤ 16 years of age must have Lansky scale ≥ 50%; or ECOG performance status ≤ 2.
- Prior Therapy
- No limit to the number of prior therapies.
- Prior Therapy Wash-out: At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives. Radiation therapy must have been completed at least 3 weeks prior to enrollment, with the exception that there is no time restriction if the subject has measurable/evaluable disease outside the radiation port or the site of radiation has documented progression.
- Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)
- ANC ≥ 750/uL*
- Platelet count ≥ 75,000/uL*
- Absolute lymphocyte count ≥ 150/uL*
- Adequate renal, hepatic, pulmonary and cardiac function defined as:
- Creatinine within institutional norms for age(i.e. ≤ 2 mg/dL in adults or according to table below in children <18 years) OR creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min
- Age (Years) Maximum \& Serum Creatinine (mg/dL):
- Age (Years): ≤5 \& Maximum Serum Creatinine (mg/dL): 0.8 Age (Years): 5 < age ≤ 10 Maximum Serum Creatinine (mg/dL): 1.0 Age (Years): >10-18 Maximum Serum Creatinine (mg/dL): 1.2 Age (Years): > 18 Maximum Serum Creatinine (mg/dL): 2.0
- Serum ALT/AST ≤ 2.5x ULN (unless elevated ALT/AST is associated with disease involvement of the liver, in which case this criterion will be waived and not disqualify a patient).
- Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.
- Cardiac ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an ECHO,
- No clinically significant ECG findings
- No clinically significant pleural effusion
- Baseline oxygen saturation > 92% on room air
- if cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); A subject will not be excluded because of pancytopenia ≥ Grade 3 if it is due to disease, based on the results of bone marrow studies.
- Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).
- Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative regimen or for as long as CART cells are detectable in peripheral blood.
- Must provide informed consent. For subjects <18 years old, or adults with limited decision-making capacity, their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and assent will be obtained for those > 7 years of age, when appropriate. If a minor becomes of age during participation of this study, he/she will be asked to reconsent as an adult.
Who cannot join
- Receiving any other current investigational agents.
- History of other malignancy, except non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast), unless disease free for at least 3 years.
- Presence of untreated brain metastases will be excluded. Subjects with previous CNS tumor involvement that has been treated and is stable for at least 3 months following completion of therapy are permitted. Patients who are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits, and no progression of residual brain abnormalities without specific therapy, are permitted.
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
- Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti HCV positive) as the immunosuppression contained in this study will pose unacceptable risk. A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
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- Any medical condition that in the judgement of the sponsor investigator is likely to interfere with assessment of safety or efficacy of study treatment.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Pregnant females are excluded from this study because the effects of autologous B7-H3CART on the developing human fetus are unknown and because the chemotherapy agents used in this trial (cyclophosphamide and fludarabine) are category D agents with the potential for teratogenic or abortifacient effects. Additionally, because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with cyclophosphamide/fludarabine, breastfeeding should be discontinued if the mother is treated with cyclophosphamide/fludarabine. These potential risks may also apply to other agents used in this study.
- Primary immunodeficiency or history of systemic autoimmune disease (e.g., Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
- Patients who require systemic corticosteroid or other immunosuppressive therapy. (A one-week washout from systemic corticosteroid or other immunosuppressive therapy is permitted.) Use of physiologic doses of corticosteroids (up to 3 mg/m2/day prednisone equivalent) are permitted. Use of topical, ocular, intra-articular, intra-nasal, or inhaled corticosteroids are permitted.
- In the investigator's judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Stanford University
Palo Alto, California, 94304
Amy Li, 650-497-8953, solidtumorcart@stanfordchildrens.org
Sneha Ramakrishna, MD
About this study
Official title: Phase I Clinical Trial of Autologous B7-H3 Chimeric Antigen Receptor T Cells (B7-H3CART) in Children and Young Adults With Relapsed or Refractory Solid Tumor Expressing B7-H3 Target
The purpose of this study is to test the manufacturing feasibility and safety of intravenous (IV) administration of B7-H3CART in children and young adult subjects with relapsed and/or refractory solid tumors expressing B7-H3 target using a standard 3+3 dose escalation design.
- Conditions
- Neuroblastoma, Sarcoma, Osteosarcoma
- Being tested
- B7-H3CART Dose (Intravenous)
- Keywords
- Chimeric Antigen Receptor, Autologous T-Cells
- Medical subject headings
- Neuroblastoma, Sarcoma, Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
B7-H3CART Dose (Intravenous)Drug
Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0.
Dose level -1 (DL-1) 0.3 x 106 transduced T cells/kg
Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0.
Dose level 1 (DL1) 1 x 106 transduced T cells/kg
Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0.
Dose level 2 (DL2) 3 x 106 transduced T cells/kg
Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0.
Dose level 2 (DL2) 3 x 106 transduced T cells/kg
Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0.
Dose level 3 (DL3) 9 x 106 transduced T cells/kg
| Study group | Role | What they receive |
|---|---|---|
| Lymphodepletion | Experimental | Fludarabine 30 mg/m2 per day IV for 4 days: 5, -4, 3, -2 Cyclophosphamide 500 mg/m2 per day IV for 3 days: -5, -4, -3 Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Receives: Drug: B7-H3CART Dose (Intravenous) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of manufacturing autologous T cells
Feasibility of manufacturing autologous T cells transduced with Ef1a-CAR276 lentiviral vector expressing B7-H3 Chimeric Antigen Receptor (B7-H3-CART), using the Miltenyi CliniMACS Prodigy® system with dasatinib and protamine sulfate.
Measured: 2 years
Safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of a single dose of intravenous B7-H3CART
Assess the safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of a single dose of intravenous B7-H3CART in children and young adults with relapsed and refractory solid tumors (i.e. soft tissue sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma) using the proposed dose escalation schedule.
Measured: 2 years
Secondary outcomes (2)
Clinical response in children and young adults
Assess clinical response in children and young adults with relapsed and refractory solid tumors treated with IV B7-H3CART.
Measured: 2 years
Safety of B7-H3CART at the MTD/RP2D
Assess the safety of B7-H3CART at the MTD/RP2D in children and young adults with relapsed and refractory solid tumors treated with IV B7-H3CART.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2024
- Study start11 Jul 2024
- Primary completionJul 2029 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sneha Ramakrishna, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06500819
- Sponsor's protocol ID
- IRB-74070
- Other IDs
- NCI-2025-00267
- Status last verified
- May 2026
- First submitted
- 8 Jul 2024
- Last updated
- 7 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of Autologous B7-H3 Chimeric Antigen Receptor T Cells (B7-H3CART) in Children and Young Adults With Relapsed or Refractory Solid Tumor Expressing B7-H3 Target
- ClinicalTrials.gov ID
- NCT06500819
- Acronym / sponsor ID
- IRB-74070
- Conditions
- Neuroblastoma, Sarcoma, Osteosarcoma
- Keywords
- Chimeric Antigen Receptor, Autologous T-Cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 11 Jul 2024 (actual)
- Primary completion
- Jul 2029 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 15 Jul 2024 (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.
The purpose of this study is to test the manufacturing feasibility and safety of intravenous (IV) administration of B7-H3CART in children and young adult subjects with relapsed and/or refractory solid tumors expressing B7-H3 target using a standard 3+3 dose escalation design.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lymphodepletion | Experimental | Drug: B7-H3CART Dose (Intravenous)Fludarabine 30 mg/m2 per day IV for 4 days: 5, -4, 3, -2 Cyclophosphamide 500 mg/m2 per day IV for 3 days: -5, -4, -3 Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. |
Who may qualify
- Ages
- 2 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (31 listed)
- Histologically confirmed malignant solid tumor (including neuroblastoma, soft tissue sarcoma, osteosarcoma, Ewing Sarcoma, and Wilms tumor) with evidence of incurable disease and tumor recurrence/progression after all available curative standard therapies.
- Subjects during dose escalation must have evaluable or measurable disease. Subjects during dose expansion must have measurable disease, except neuroblastoma which may have MIBG positive disease only.
- B7-H3 positive expression on malignant cells is NOT required but archival tissue must be available, or the subject must be willing to undergo tissue biopsy for expression analysis.
- Age: Must be ≥ 2 and ≤ 30 years of age.
- Performance Status: Patients > 16 years of age must have Karnofsky ≥ 50%. Patients ≤ 16 years of age must have Lansky scale ≥ 50%; or ECOG performance status ≤ 2.
Key exclusion criteria (12 listed)
- Receiving any other current investigational agents.
- History of other malignancy, except non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast), unless disease free for at least 3 years.
- Presence of untreated brain metastases will be excluded. Subjects with previous CNS tumor involvement that has been treated and is stable for at least 3 months following completion of therapy are permitted. Patients who are clinically stable as evidenced by no requirements for corticosteroids, no evolving neurologic deficits, and no progression of residual brain abnormalities without specific therapy, are permitted.
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
- Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti HCV positive) as the immunosuppression contained in this study will pose unacceptable risk. A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
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 |
|---|---|---|
| B7-H3CART Dose (Intravenous)Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level -1 (DL-1) 0.3 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 1 (DL1) 1 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 2 (DL2) 3 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 2 (DL2) 3 x 106 transduced T cells/kg Subjects who meet cell infusion eligibility will receive IV B7-H3CART cells on Day 0. Dose level 3 (DL3) 9 x 106 transduced T cells/kg | Drug | Lymphodepletion |
Primary outcome
Feasibility of manufacturing autologous T cells
Time frame: 2 years
Feasibility of manufacturing autologous T cells transduced with Ef1a-CAR276 lentiviral vector expressing B7-H3 Chimeric Antigen Receptor (B7-H3-CART), using the Miltenyi CliniMACS Prodigy® system with dasatinib and protamine sulfate.
Safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of a single dose of intravenous B7-H3CART
Time frame: 2 years
Assess the safety and identify the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of a single dose of intravenous B7-H3CART in children and young adults with relapsed and refractory solid tumors (i.e. soft tissue sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma) using the proposed dose escalation schedule.
2 secondary outcomes
Clinical response in children and young adults
Time frame: 2 years
Safety of B7-H3CART at the MTD/RP2D
Time frame: 2 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 7 May 2026.
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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.
Sneha Ramakrishna, MD principal investigator
Stanford University
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 B7-H3CART Dose (Intravenous) in people with Neuroblastoma and Sarcoma, run by Stanford University 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 31 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 7 May 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?
Contact Amy Li (650-497-8953, solidtumorcart@stanfordchildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of manufacturing autologous T cells (time frame: 2 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 7 May 2026.