Atypical Teratoid Rhabdoid TumorPhase 1NCT07513194
GPC3 CAR T Cells With IL-15 and IL-21 for Recurrent ATRT and CNS Rhabdoid Tumors (RADIANT)
A Phase 1 study testing 21.15.GPC3-CAR T Cells in people with Atypical Teratoid Rhabdoid Tumor and Central Nervous System Rhabdoid Tumor, run by Baylor College of Medicine at 1 site in United States.
Trial summary
This study is being conducted in patients with GPC3-positive brain tumors that have recurred or have not responded to standard therapy. Atypical teratoid rhabdoid tumors (ATRT) are aggressive tumors with poor outcomes and limited treatment options, particularly in young children. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Atypical Teratoid Rhabdoid Tumor, Central Nervous System Rhabdoid Tumor
- What is being tested?
- 21.15.GPC3-CAR T Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2026to 31 Oct 2044
- 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 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Procurement Inclusion Criteria:
- 1) Diagnosis of GPC3-positive recurrent ATRT.
- 2) Age ≥ 6 months
- 3) Karnofsky/Lansky score ≥ 60%
- 4) Informed consent explained to, understood by, and signed by patient/guardian; copy provided
- 5) GPC3 expression by immunohistochemistry with extent score ≥ Grade 2 (>25% positive tumor cells) and intensity score ≥ 2 (scale 0-4)
Procurement Exclusion Criteria:
- 1) No history of organ transplantation
- 2) No known HIV positivity
- 3) No active bacterial, fungal, or viral infection (except Hepatitis B or Hepatitis C virus infections)
- 4) No other risk factors in which administration of the investigational agent is deemed not in the patient's best interest, in the opinion of the investigator
Treatment Inclusion Criteria:
- 1) Age ≥ 6 months
- 2) Diagnosis of treatment refractory or unresectable ATRT after standard of care therapy
- 3) Lansky/Karnofsky score ≥ 60%
- 4) Stable neurologic exam for 7 days prior to enrollment
- 5) Stable or decreasing dose of steroids over past 7 days prior to surgery and administration of therapy (max allowable dose is 0.1mg/kg dexamethasone or equivalent per day)
- 6) Not receiving any concurrent anti-cancer therapy.
- 7) At least 6 weeks following craniospinal radiation therapy.
- 8) At least 14 days wash-out needed following small volume radiotherapy (i.e., Stereotactic Radiosurgery (SRS)).
- 9) At least 21 days or 5 half-lives (whichever is shorter) must have elapsed since any prior systemic therapy
- 10) Received any other forms of immunotherapy ≤ 42 days before administration of investigational agent
- 11) At least 28 days following bevacizumab
- 12) Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
- 13) Total bilirubin < 3 times ULN for age
- 14) INR ≤ 1.7
- 15) Absolute neutrophil count > 500/μl
- 16) Platelet count > 100,000/μl (can be transfused but must be achieved prior to enrollment)
- 17) Hgb ≥ 7.0 g/dl (can be transfused)
- 18) Pulse oximetry > 90% on room air
- 19) Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study
- 20) Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.
- 21) Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
Treatment Exclusion Criteria:
- 1) Pregnancy or lactation (for women at child-bearing age, birth control is required)
- 2) Uncontrolled infection
- 3) Known HIV positivity
- 4) Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)
- 5) History of organ transplantation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Ramy Sweiden contact
United States1 site
Texas Children's Hospital
Houston, Texas, 77030
David Steffin, MD, (832) 824-4233, dhsteffi@texaschildrens.org
About this study
Official title: Robust Armored Dual-Cytokine (IL-15/IL-21) GPC3-CAR T Cells for Atypical Teratoid Rhabdoid Tumors and Central Nervous System Rhabdoid Tumors (RADIANT)
This study is being conducted in patients with GPC3-positive brain tumors that have recurred or have not responded to standard therapy. Atypical teratoid rhabdoid tumors (ATRT) are aggressive tumors with poor outcomes and limited treatment options, particularly in young children. There is a need for new therapies that can improve outcomes while minimizing toxicity.
This study evaluates a new experimental treatment using genetically engineered T cells (RADIANT-T cells) that target glypican-3 (GPC3), a protein expressed on tumor cells. These T cells are modified to express a chimeric antigen receptor (CAR) targeting GPC3, along with IL-15 and IL-21 to enhance their persistence and activity. The cells also include an inducible safety mechanism (iCasp9) that allows them to be eliminated if necessary.
The purpose of this study is to determine the highest safe dose of RADIANT-T cells, evaluate their safety and side effects, assess how long they persist in the body, and determine whether they show anti-tumor activity in patients with GPC3-positive brain tumors.
Read the detailed description
This is a Phase 1 dose-escalation study conducted at Texas Children's Hospital to evaluate RADIANT-T cells in patients with GPC3-positive brain tumors. Approximately 15-24 subjects will participate in the treatment portion of the study.
Autologous T cells are collected from the patient and genetically engineered using a retroviral vector to express a GPC3-specific chimeric antigen receptor along with IL-15 and IL-21. The modified T cells are expanded and tested for activity against GPC3-positive tumor cells prior to administration.
Patients receive a single dose of RADIANT-T cells administered intracavitarily during a planned surgical resection. Prior to administration, patients may receive premedication to reduce the risk of infusion reactions. During surgery, an Ommaya reservoir is placed to allow monitoring and management of potential treatment-related effects.
This is a dose-escalation study in which groups of patients receive increasing dose levels of RADIANT-T cells to determine the maximum tolerated dose. The dose administered to each patient depends on prior patient outcomes at lower dose levels.
Patients undergo clinical evaluations before treatment, including physical examination, laboratory testing, and imaging studies. After treatment, patients are monitored with physical exams, laboratory tests, cerebrospinal fluid assessments, and imaging to evaluate safety and tumor response.
Tumor assessments are performed by MRI at approximately 1 week and 4-6 weeks after treatment. Patients are followed longitudinally to assess safety, persistence of the modified T cells, and clinical outcomes. Long-term follow-up continues for up to 15 years after infusion, with more frequent visits early after treatment and less frequent visits over time.
- Being tested
- 21.15.GPC3-CAR T Cells
- Keywords
- CAR T Cell Therapy, GPC3 CAR T Cells, Glypican-3, Atypical Teratoid Rhabdoid Tumor, CNS Rhabdoid Tumor, Pediatric Brain Tumor, Adoptive Cellular Immunotherapy, Intracerebroventricular Immunotherapy, Solid Tumor CAR T Therapy
- Medical subject headings
- Rhabdoid Tumor, Simpson-Golabi-Behmel syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
21.15.GPC3-CAR T CellsBiological
Also called RADIANT-T cells
Autologous T cells genetically engineered using retroviral vectors encoding a GPC3-specific CAR and IL-15 and IL-21 cytokines. The product also includes an inducible caspase-9 safety switch allowing pharmacologic elimination of the CAR T cells in the event of severe toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with 21.15.GPC3-CAR T Cell Therapy (RADIANT CAR T Cells) | Experimental | Participants will receive autologous 21.15.GPC3-CAR T cells administered intratumorally into the tumor resection cavity and/or intracerebroventricularly via an Ommaya reservoir. CAR T cells are genetically engineered using retroviral vectors encoding a GPC3-specific chimeric antigen receptor and cytokines IL-15 and IL-21.
The following dose levels of CAR T cells will be evaluated:
* DL0: 1 × 10⁷ CAR T cells
* DL1: 3 × 10⁷ CAR T cells
* DL2: 5 × 10⁷ CAR T cells
* DL3: 1 × 10⁸ CAR T cells
If dose de-escalation from DL1 is required, patients will be treated at DL0. Further de-escalation may use half-log reductions if needed. Dose escalation will occur only after safety evaluation of prior cohorts. Receives: Biological: 21.15.GPC3-CAR T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Dose-Limiting Toxicity
DLT will be defined as any of the following that may be considered possibly, probably, or definitely related to the 21.15.GPC3-CAR T cells: Any Grade 5 event, Non-hematologic dose-limiting toxicity (any Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours), Grade 4 allergic reaction to CAR T cell administration, Grade 4 reactions due to CRS and neurotoxicity (rarely seen with the use of CAR-based immunotherapy), Grade 3 cytokine release syndrome (CRS) infusion reactions and neurologic toxicity that fail to return to Grade 1 within 72 hours, Grade 4 CRS and neurologic toxicities
Measured: 4 weeks after CAR T-cell administration
Secondary outcomes (2)
Maximum Tolerated Dose (MTD) of intratumoral and/or ICV injection of 21.15.GPC3-CAR T cells in treating patients with GPC3-positive recurrent or incompletely resected ATRT.
Once dose escalation is finished and all patients are evaluable for DLT, we will determine the MTD based on isotonic regression, specifically, the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there is no DLT that determine a MTD, the maximum dose level will be declared as the MTD. In case the lowest dose level is determined to be too toxic and the elimination boundary is reached, no MTD will be defined for the trial.
Measured: 28 days
Response Rate
Response rates will be estimated as the percent of patients whose best response is either complete response or partial response by combining the data from lesions recorded via imaging for each patient pre- and post- 21.15.GPC3-CAR T-cell intratumoral and/or ICV injection.
Per immunotherapy response assessment for neuro-oncology (iRANO) criteria:
- Complete Response (CR): Disappearance of all enhancing disease for ≥4 weeks; no new lesions; stable or improved T2/FLAIR; no more than physiological steroids; clinically stable or improved.
- Partial Response (PR): ≥50% decrease in the sum of biperpendicular diameters of enhancing disease for ≥4 weeks; no new lesions; stable or improved T2/FLAIR; stable or decreased steroid dose; clinically stable or improved.
Measured: 4-6 weeks after CAR T-cell administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2026
- Study start1 Sep 2026 (estimated)
- Primary completion31 Oct 2029 (estimated)
- Study completion31 Oct 2044 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atypical Teratoid Rhabdoid TumorStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Steffin, MD, Baylor College of Medicine
- Investigators
- David Steffin, MD, Principal investigator, Baylor College of MedicineJasia Mahdi, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07513194
- Sponsor's protocol ID
- H-58806, RADIANT
- Status last verified
- Apr 2026
- First submitted
- 1 Apr 2026
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Robust Armored Dual-Cytokine (IL-15/IL-21) GPC3-CAR T Cells for Atypical Teratoid Rhabdoid Tumors and Central Nervous System Rhabdoid Tumors (RADIANT)
- ClinicalTrials.gov ID
- NCT07513194
- Acronym / sponsor ID
- H-58806, RADIANT
- Keywords
- CAR T Cell Therapy, GPC3 CAR T Cells, Glypican-3, Atypical Teratoid Rhabdoid Tumor, CNS Rhabdoid Tumor, Pediatric Brain Tumor, Adoptive Cellular Immunotherapy, Intracerebroventricular Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 31 Oct 2029 (estimated)
- Study completion
- 31 Oct 2044 (estimated)
- First posted
- 7 Apr 2026 (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 study is being conducted in patients with GPC3-positive brain tumors that have recurred or have not responded to standard therapy. Atypical teratoid rhabdoid tumors (ATRT) are aggressive tumors with poor outcomes and limited treatment options, particularly in young children. There is a need for new therapies that can improve outcomes while minimizing toxicity.
This study evaluates a new experimental treatment using genetically engineered T cells (RADIANT-T cells) that target glypican-3 (GPC3), a protein expressed on tumor cells. These T cells are modified to express a chimeric antigen receptor (CAR) targeting GPC3, along with IL-15 and IL-21 to enhance their persistence and activity. The cells also include an inducible safety mechanism (iCasp9) that allows them to be eliminated if necessary.
The purpose of this study is to determine the highest safe dose of RADIANT-T cells, evaluate their safety and side effects, assess how long they persist in the body, and determine whether they show anti-tumor activity in patients with GPC3-positive brain tumors.
Detailed description
This is a Phase 1 dose-escalation study conducted at Texas Children's Hospital to evaluate RADIANT-T cells in patients with GPC3-positive brain tumors. Approximately 15-24 subjects will participate in the treatment portion of the study.
Autologous T cells are collected from the patient and genetically engineered using a retroviral vector to express a GPC3-specific chimeric antigen receptor along with IL-15 and IL-21. The modified T cells are expanded and tested for activity against GPC3-positive tumor cells prior to administration.
Patients receive a single dose of RADIANT-T cells administered intracavitarily during a planned surgical resection. Prior to administration, patients may receive premedication to reduce the risk of infusion reactions. During surgery, an Ommaya reservoir is placed to allow monitoring and management of potential treatment-related effects.
This is a dose-escalation study in which groups of patients receive increasing dose levels of RADIANT-T cells to determine the maximum tolerated dose. The dose administered to each patient depends on prior patient outcomes at lower dose levels.
Patients undergo clinical evaluations before treatment, including physical examination, laboratory testing, and imaging studies. After treatment, patients are monitored with physical exams, laboratory tests, cerebrospinal fluid assessments, and imaging to evaluate safety and tumor response.
Tumor assessments are performed by MRI at approximately 1 week and 4-6 weeks after treatment. Patients are followed longitudinally to assess safety, persistence of the modified T cells, and clinical outcomes. Long-term follow-up continues for up to 15 years after infusion, with more frequent visits early after treatment and less frequent visits over time.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with 21.15.GPC3-CAR T Cell Therapy (RADIANT CAR T Cells) | Experimental | Biological: 21.15.GPC3-CAR T CellsParticipants will receive autologous 21.15.GPC3-CAR T cells administered intratumorally into the tumor resection cavity and/or intracerebroventricularly via an Ommaya reservoir. CAR T cells are genetically engineered using retroviral vectors encoding a GPC3-specific chimeric antigen receptor and cytokines IL-15 and IL-21. The following dose levels of CAR T cells will be evaluated: * DL0: 1 × 10⁷ CAR T cells * DL1: 3 × 10⁷ CAR T cells * DL2: 5 × 10⁷ CAR T cells * DL3: 1 × 10⁸ CAR T cells If dose de-escalation from DL1 is required, patients will be treated at DL0. Further de-escalation may use half-log reductions if needed. Dose escalation will occur only after safety evaluation of prior cohorts. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| 21.15.GPC3-CAR T CellsAlso: RADIANT-T cellsAutologous T cells genetically engineered using retroviral vectors encoding a GPC3-specific CAR and IL-15 and IL-21 cytokines. The product also includes an inducible caspase-9 safety switch allowing pharmacologic elimination of the CAR T cells in the event of severe toxicity. | Biological | Treatment with 21.15.GPC3-CAR T Cell Therapy (RADIANT CAR T Cells) |
Primary outcome
Number of Participants with Dose-Limiting Toxicity
Time frame: 4 weeks after CAR T-cell administration
DLT will be defined as any of the following that may be considered possibly, probably, or definitely related to the 21.15.GPC3-CAR T cells: Any Grade 5 event, Non-hematologic dose-limiting toxicity (any Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours), Grade 4 allergic reaction to CAR T cell administration, Grade 4 reactions due to CRS and neurotoxicity (rarely seen with the use of CAR-based immunotherapy), Grade 3 cytokine release syndrome (CRS) infusion reactions and neurologic toxicity that fail to return to Grade 1 within 72 hours, Grade 4 CRS and neurologic toxicities
2 secondary outcomes
Maximum Tolerated Dose (MTD) of intratumoral and/or ICV injection of 21.15.GPC3-CAR T cells in treating patients with GPC3-positive recurrent or incompletely resected ATRT.
Time frame: 28 days
Response Rate
Time frame: 4-6 weeks after CAR T-cell administration
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 Apr 2026.
- Individual participant dataSharing planned: No
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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.
Ramy Sweiden contact
David Steffin, MD principal investigator
Baylor College of Medicine
Jasia Mahdi, MD principal investigator
Baylor College of Medicine
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 21.15.GPC3-CAR T Cells in people with Atypical Teratoid Rhabdoid Tumor and Central Nervous System Rhabdoid Tumor, run by Baylor College of Medicine 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?
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: opening soon, as of the sponsor's last update on 7 Apr 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 David Steffin, MD ((832) 824-4233, dhsteffi@texaschildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Dose-Limiting Toxicity (time frame: 4 weeks after CAR T-cell administration). 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 Apr 2026.