Engineered immune cells delivered directly to the brain show promise for kids with deadly tumors
NCT ID NCT05835687
First seen Jun 27, 2026 · Last updated Jul 07, 2026 · Updated 2 times
Summary
This early-stage trial tests a new treatment for children and young adults up to age 21 with certain brain tumors that have come back or not responded to standard therapy. The treatment uses the patient's own immune cells, which are modified in a lab to recognize and attack a protein called B7-H3 found on tumor cells. These cells are delivered directly into the fluid around the brain through a small tube. The main goal is to find the safest dose and see if the treatment can shrink tumors.
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Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1
The first testing in people. Mainly checks safety and dose, usually in a small group.
- Participants
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29 people
The number who actually took part.
- Started
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Apr 2023
- Expected to finish
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Mar 2028
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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Up to 21 years
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: Screening Eligibility 1. Age ≤ 21 years of age 2. Primary CNS tumor 3. For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor 4. For Cohort B, must meet one of the following criteria: * Adequate tumor tissue from primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry \[IHC\] or H3K27M mutation if pontine lesion) * Has a diagnosis of diffuse midline glioma that harbors a mutation associated with this entity (e.g. H3K27M) * Has presumptive/suspected brainstem high-grade neoplasm with available imaging for central imaging review 5. Life expectancy of \> 12 weeks 6. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines Exclusion Criteria: Screening Eligibility All Participants 1\. Participant has other clinically significant medical disorders (e.g. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with study procedure. Inclusion Criteria: Procurement and T-cell Production Eligibility 1. Age ≤ 21 years of age 2. Primary CNS tumor with measurable or evaluable disease and meets criteria for either Cohort A or B: * Cohort A: relapsed/refractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive * Cohort B: Diffuse midline glioma AND tumor is: * B7-H3 positive if non-pontine * OR H3K27-altered diffuse midline pontine glioma * OR radiographically-confirmed classic/typical DIPG 3. Estimated life expectancy of \>12 weeks 4. Karnofsky or Lansky performance score ≥50 5. Participant of childbearing/child-fathering potential agrees to use contraception 6. For females of childbearing age: * Not pregnant with negative serum pregnancy test * Not lactating with intent to breastfeed 7. Chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment 8. The last dose of antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment 9. At least 30 days from most recent cell infusion prior to enrollment. 10. All systemically administered corticosteroid therapy must be stable or decreasing for ≥1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m\^2/day 11. Meets eligibility for apheresis, or has an apheresis product previously collected at a FACT-accredited program 12. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines Exclusion Criteria: Procurement and T-cell Production Eligibility 1. Known primary immunodeficiency or acquired immunodeficiency. 2. Known HIV positivity 3. Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection). 4. Rapidly progressive disease 5. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments. 6. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study. Inclusion Criteria: Treatment Eligibility Cohort A * Relapsed/refractory non-brainstem CNS primary tumor * Tumor must be considered B7-H3 positive Cohort B * Diffuse Midline Glioma - Must meet one of the following criteria * Tumor is considered B7-H3 positive * H3K27-altered diffuse midline pontine glioma * Radiographically-confirmed classic/typical DIPG * Must complete standard radiation prior to Loc3CAR treatment and be a minimum of 6 weeks post-completion of radiation therapy All participants 1. Age ≤ 21 years old 2. Primary CNS tumor with measurable or evaluable disease 3. Available autologous T-cell product that has met GMP release criteria 4. Participant has a CNS reservoir catheter (e.g., Ommaya) or programmable shunt 5. First CAR T cell infusion is planned/scheduled ≥ 5 days from CNS surgery, including catheter placement 6. The following treatments must be discontinued for the specified duration prior to treatment enrollment: * Radiation therapy: ≥ 6 weeks * Bevacizumab: ≥ 28 days * Cytotoxic chemotherapy: ≥ 21 days * Biologic agents: ≥ 7 days * Antibody therapy: ≥ 3 half-lives or 30 days (whichever is shorter) * Cellular therapy: ≥ 30 days * Investigational agent: ≥ 3 half-lives or 30 days (whichever is shorter) * Corticosteroids: All systemically administered therapy must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m\^2/day. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed. 7. Estimated life expectancy of \>8 weeks 8. Karnofsky or Lansky performance score ≥ 50 9. Echocardiogram with a left ventricular ejection fraction ≥ 50% 10. Adequate renal function defined as calculated creatinine clearance or radioisotope GFR ≥ 50 mL/min/1.73m\^2. 11. Adequate pulmonary function defined as forced vital capacity (FVC) ≥50% of predicted value or pulse oximetry ≥90% on room air. 12. Total Bilirubin ≤3 times the upper limit of normal for age. 13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age. 14. Hemoglobin \>8.0 g/dL (can be transfused). 15. Platelet count \>50,000/mm\^3 (can be transfused). 16. Absolute neutrophil count (ANC) ≥1000/uL. 17. Taking anti-seizure medication, or agrees to initiate anti-seizure medication prior to starting study therapy. 18. Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy. 19. Male participants of child-fathering potential agree to use contraception 20. Female participants of childbearing potential: * Negative serum pregnancy test within 7 days prior to infusion * Not lactating with intent to breastfeed * If sexually active, agrees to use birth control until 3 months after T-cell infusion. Male partners should use a condom 21. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines Exclusion Criteria: Treatment Eligibility-All Participants 1. Participant has a non-programmable ventricular shunt that could compromise study therapy 2. Participant has a reservoir catheter or shunt in a location that could compromise study therapy or patient safety 3. Known primary immunodeficiency or acquired immunodeficiency. 4. Known HIV positivity 5. Severe intercurrent bacterial, viral or fungal infection 6. Myocardial infarction, unstable angina, New York Heart Association class III and IV congestive heart failure, myocarditis, or ventricular arrhythmias requiring medication within 6 months prior to study entry 7. Receiving therapy as outlined above during the 'wash-out' period 8. Rapidly progressing disease 9. Received any live vaccines within 30 days 10. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments 11. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study 12. Evidence of uncontrolled hypertension. Anti-hypertensive medications are permitted if on a stable dose. 13. Uncontrolled seizures
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
Contacts and locations
Locations
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St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
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Other studies related to the condition(s) this trial covers.
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