A Phase 1 interventional study of Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) and Group A Standard-of-Care Backbone Therapy in Medulloblastoma, Childhood, Atypical Teratoid/Rhabdoid Tumor of CNS and Embryonal Tumor With Multilayered Rosettes, sponsored by Children's National Research Institute. Recruiting at 1 site in United States. Open to participants aged 1 Year to 30 Years. Per ClinicalTrials.gov, last updated 2026-10-13.
Sponsored by Children's National Research Institute · Phase 1, Interventional, and Treatment
This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) derived from a patient's primary brain tumor tissues. Young patients with embryonal central nervous system (CNS) malignancies typically are unable to receive irradiation due to significant adverse effects and are treated with intensive chemotherapy followed by autologous stem cell rescue; however, despite intensive therapy, many of these patients relapse. Patients with recurrent ependymoma have a poor survival and this disease has a dearth of targetable molecular features. In this study, individualized TSA-T cells will be generated against proteogenomically determined tumor-specific antigens after standard of care treatment in children less than 5 years of age with embryonal brain tumors (Arm A) and children with recurrent ependymoma (Arm B).
Correlative biological studies will measure clinical anti-tumor, immunological and biomarker effects.
TSA-T products will be manufactured at the cell therapy Good Manufacturing Practice (GMP) facility at Children's National Hospital (CNH). Patients enrolled in the study will receive their infusions at CNH.
This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA), derived from a patient's primary brain tumor tissues. Participants in this study will receive TSA-T after completion of standard-of-care/salvage therapy for either their newly diagnosed embryonal brain tumor or their recurrent ependymoma. Participants will be enrolled into one of two Groups:
Group B: Children, adolescents and young adults greater than 1 year and less than 30 years of age with recurrent ependymoma (EPN).
Group A Standard-of-Care Backbone Therapy: Patients will undergo surgical resection, then be treated with standard-of-care therapy as required, which may include up to 3 induction chemotherapy cycles (vincristine, cyclophosphamide, cisplatin, etoposide with or without methotrexate) and up to 3 consolidation cycles (carboplatin and thiotepa, each followed by an infusion of autologous peripheral blood stem cells (PBSCs)). Please note: Methotrexate may be part of the induction chemotherapy, and radiation may be added during backbone therapy, as per treating physician's discretion.
Group B Salvage Backbone Therapy: Patients will undergo surgical re-resection - aiming for gross total resection when feasible - followed by re-irradiation. Re-irradiation may be delivered as a conventional fractionated course, hypofractionated stereotactic radiotherapy, or proton therapy, depending on prior treatments, institutional guidelines and treating physician's discretion. Bridging chemotherapy may be administered between re-irradiation and TSA-T cell infusion, or instead of re-irradiation, at the treating physician's discretion.
Patients will receive the TSA-T product at assigned dose levels as per the table and details below until the highest planned dose level or the MTD is reached. The MTD will be declared when prespecified stopping/escalation rules and DLT data allow a determination, and the recommended phase 2 dose (RP2D) will be established using the MTD together with additional safety, tolerability and pharmacodynamic data.
Dose Levels TSA-T cell dose -1 1x107 cells 1* 2.5x107 cells 2 5x107 cells
*Starting dose
The MTD and RP2D determinations, as well as all dose escalation and de-escalation decisions, will be based on pooled safety data from Groups A and B combined. However, the secondary objectives pertaining to objective tumor response and clinical survival, will be analyzed separately for Group A and Group B.
Safety will be assessed at two planned TSA-T dose levels, 2.5×10⁷ and 5×10⁷ cells, with the option to de-escalate to 1×10⁷ cells if warranted. Dose escalation will follow a Bayesian optimal interval (BOIN) design with a 42-day DLT monitoring period. An interim safety analysis will be conducted after the first six patients.
Each patient will receive at least one TSA-T infusion and may receive a maximum of 8 total infusions if they remain eligible and sufficient TSA-T cells are available. All infusions will be intracerebroventricularly (ICV) administered through the protocol-required Rickham reservoir.
For any infusion following the first infusion, if a patient's remaining cryopreserved TSA-T product is insufficient to meet the dose at the enrollment dose level, the final infusion may be administered at a lower available dose at the discretion of study PI.
If patients have a response of stable disease or better by RAPNO criteria at the evaluation after the second infusion OR if they have clinical stability and a clinical assessment of possible pseudoprogression (per iRANO) on MRI despite the appearance of radiographic progression (with subsequent serial MRI findings most consistent with pseudoprogression), they may be eligible to receive additional infusions of TSA-T.
The first and second infusions will be administered at least 42 days apart and additional infusions will be spaced at least 28 days apart. Once a patient begins TSA-T treatment, and until they are taken off treatment, they are expected to adhere to the protocol-defined treatment schedule as closely as possible, with approximately two weeks of flexibility beyond the minimum required infusion interval. The exception is in cases of suspected pseudoprogression (PsP), where an extended interval of up to eight weeks beyond the minimum interval may be permitted to allow for repeat imaging prior to additional TSA-T infusion(s).
Prior to the first infusion, if a patient's cryopreserved TSA-T product is insufficient for the dose level that the patient is assigned to, the patient may receive TSA-Ts at a lower dose level with a minimum of 1x107 cells. These patients will not count towards the overall safety objective, although they will count towards the feasibility objective of identifying TSAs and producing adequate TSA-T products.
317 studies on the registry are indexed under Medulloblastoma; 51 are open to participants now.
This study's planned enrollment of 12 is below the median of 31 across 255 interventional studies indexed under Medulloblastoma.
Browse Medulloblastoma studies →Children's National Research Institute is the lead sponsor of 127 studies on the registry; 47 are open to participants now.
Counted across the registry records on this site, refreshed daily.
RECIPIENT SCREENING INCLUSION CRITERIA
Diagnosis (select one group):
Age:
Tissue:
o Group A: Availability of sufficient fresh or frozen tumor tissue (approximately 50 mg).
o Group B: Expectation of sufficient fresh or frozen tumor tissue, in the opinion of study PI or sub-I (based upon radiographic evidence of disease).
Non-pregnant:
Common to both groups:
Adequate organ function, defined below:
i. ≥750/µL. ii. Absolute lymphocyte count (ALC) >500/μL. iii. ≥75K. iv. ≤3xULN. v. (AST) and Alanine aminotransferase (ALT) \<5x (ULN).
vi. Serum creatinine ≤1.0 mg/dL or 1.5x ULN for age (whichever is higher). vii. Pulse oximetry >90% on room air.
RECIPIENT INCLUSION CRITERIA FOR PROCUREMENT
1. Karnofsky or Lansky score of ≥60%. 2. Adequate organ function, defined below: i. ANC ≥750/µL. ii. Absolute lymphocyte count (ALC) >500/μL. iii. Platelets ≥75K. iv. Bilirubin ≤3xULN. v. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<5x upper limit of normal (ULN).
vi. Serum creatinine ≤1.0mg/dL or 1.5x ULN for age (whichever is higher). vii. Pulse oximetry >90% on room air. 3. Non-pregnant:
RECIPIENT INCLUSION CRITERIA FOR INITIAL TSA-T ADMINISTRATION AND FOR ADDITIONAL INFUSIONS
Adequate organ function, defined as below:
i. Bilirubin ≤3x ULN. ii. AST and ALT ≤5x ULN. iii. Serum creatinine ≤1.0mg/dL or 1.5x ULN for age (whichever is higher). iv. Pulse oximetry >90% on room air.
Applicable to TSA-T Infusion #1 only: Adequate count recovery, as described below, from prior therapies:
i. Absolute Neutrophil Count (ANC) >1000/μL ii. Absolute Lymphocyte Count (ALC) >500/μL
Patients must have received their last dose of:
a. Myelosuppressive chemotherapy (if applicable) ≥14 days prior to TSA-T infusion b. Focal radiation (if applicable) ≥14 days prior to TSA-T infusion c. Craniospinal irradiation (if applicable) ≥28 days prior to TSA-T infusion
EXCLUSION CRITERIA RECIPIENT SCREENING EXCLUSION CRITERIA
1. Patients with uncontrolled infections. 2. Patients with known infection. 3. Group A patients with medulloblastoma of the SHH subtype.
RECIPIENT EXCLUSION CRITERIA FOR PROCUREMENT
1. Patients with a fever above 38.0°C. 2. Patients with known HIV infection. 3. Prior immunotherapy with an agent within the 28 days prior to planned date of procurement collection for TSA-T manufacturing.
4. Patients who will be unable to tolerate the apheresis procedure, including inability to tolerate placement of apheresis line (if applicable), in the opinion of PI or medically licensed sub-I.
5. Patients who have overly bulky tumors on imaging are ineligible. These include the following: i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study.
If, due to complications during apheresis or subsequent manufacturing, procurement is repeated at a later date using peripheral whole blood collection, exclusion criterion #4 does not apply.
RECIPIENT EXCLUSION CRITERIA FOR INITIAL AND SUBSEQUENT TSA-T INFUSIONS
Patients with progressive disease based on most recent evaluation (for subsequent infusions).
a. Patients with progressive disease based on most recent evaluation may receive initial TSA-T infusion but would be ineligible if the tumor is found to be progressive before subsequent infusions
Patients who have overly bulky tumors on imaging are ineligible. These include the following:
i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Children younger than 5 years of age with newly diagnosed embryonal brain tumors - including medulloblastoma (MB), atypical teratoid/rhabdoid tumor (ATRT), embryonal tumor with multilayered rosettes (ETMR), and embryonal brain tumor not otherwise specified (NOS).
Biological: Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) · Drug: Group A Standard-of-Care Backbone Therapy
Children, adolescents and young adults greater than 1 year and less than 30 years of age with recurrent ependymoma
Biological: Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) · Radiation: Group B Salvage Backbone Therapy
Participants in this study will receive TSA-T after completion of standard-of-care treatment.
Patients will undergo surgical resection, then be treated with standard-of-care therapy as required, which may include up to 3 induction chemotherapy cycles (vincristine, cyclophosphamide, cisplatin, etoposide with or without methotrexate) and up to 3 consolidation cycles (carboplatin and thiotepa, each followed by an infusion of autologous peripheral blood stem cells).
Patients will undergo surgical re-resection - aiming for gross total resection when feasible - followed by re-irradiation. Re-irradiation may be delivered as a conventional fractionated course, hypofractionated stereotactic radiotherapy, or proton therapy. Bridging chemotherapy may be substituted for re-irradiation or may follow re-irradiation at the treating physician's discretion.
To evaluate the safety of TSA-T in children, adolescents, and young adults with high-risk CNS embryonal and recurrent ependymoma tumors. Safety will be evaluated by the incidence of dose limiting toxicities (DLTs).
The safety endpoint will be assessed by monitoring for incidence of DLTs-defined as any of the below events occurring within 42 days following a participant's first TSA-T infusion (per CTCAE v. 6.0): * Grade ≥3 infusion-related adverse event. * Grade ≥4 non-hematologic adverse event that is not due to the patient's underlying malignancy or chemotherapy related co-morbidities. * Grade ≥3 pneumonitis, uveitis. * Grade ≥3 toxicities that are attributed to TSA-T (possibly, probably or definitely TSA-T related). * Unexpected toxicity of grade ≥3 attributed to the infusion of TSA-T (possibly, probably or definitely TSA-T related).
Time frame: 42 days of the first TSA-T infusion
To estimate the maximum-tolerated dose (MTD) of intracerebroventricularly-administered TSA-T in children, adolescents and young adults with high-risk CNS embryonal tumors and recurrent ependymoma.
The MTD will be estimated adaptively throughout the trial using Bayesian optimal interval (BOIN) design, based on incidence of DLTs. After trial completion, the final maximum tolerated dose regimen (MTDR) will be selected using isotonic regression of pooled safety data from Groups A and B.
Time frame: 42 days of the first TSA-T infusion
Feasibility of TSA identification
The number of TSA identified for each tumor will be measured. The endpoint will be the number of patients with at least 2 TSA peptides identified.
Time frame: Up to 5 years after the first TSA-T cell infusion
Feasibility of TSA-T cell generation
The time from the acquisition of tissue to the availability of manufactured TSA-T products, measured in comparison to the length of the SOC therapy regimen/s preceding the infusion (\~12-24 weeks).
Time frame: At start of SOC/Salvage therapy until start of TSA-T cell treatment (up to 24 weeks)
To record preliminary evidence of objective disease response to TSA-T cells in embryonal tumors and recurrent ependymomas, among patients with residual disease after completion of SOC or salvage treatment per protocol
Objective disease response to TSA-T cells - Patients with residual disease (at primary site or metastatic deposits) after SOC or salvage therapy regimen will be assessed for response to TSA-T according to Response Assessment in Pediatric Neuro-Oncology (RAPNO) Criteria using magnetic resonance imaging (MRI). Patients will be evaluated with appropriate modalities at all prior sites of disease and for any new sites of disease based on symptoms or imaging. Response will be defined as any patient who achieves complete response (CR), partial response (PR), or prolonged stable disease (SD).
Time frame: Up to 1 year after first TSA-T cell infusion
To record preliminary evidence of prolonged survival through analysis of progression free survival (PFS) and overall survival (OS).
Progression-free and overall survival - PFS is defined as the interval of time between the date of surgery confirming diagnosis (Group A) or date of surgery confirming recurrence (Group B) and the earliest date of documentation of progressive disease, or secondary malignancy or death (for any reason) for patients who fail; or to date of last contact or initiation of other therapy for patients who remain at risk of failure. OS is defined as the interval of time between the date of surgery confirming diagnosis (Group A) or date of surgery confirming recurrence (Group B) to date of death. PFS and OS will be analyzed by the Kaplan-Meier method and contextualized by outcomes reported in historical studies (when feasible).
Time frame: Up to 5 years after the first TSA-T cell infusion
To correlate clinical parameters (objective disease response, survival, and adverse events) with in vivo persistence of TSA-T and other measures of immune response in cerebrospinal fluid (CSF).
Correlation of PFS and OS will be descriptively correlated to measures of in vivo TSA-T cell persistence and immune activation (including cytokine/chemokine protein levels in CSF).
Time frame: Up to 5 years after the first TSA-T cell infusion
To characterize the phenotype of manufactured TSA-T cells prior to infusion and correlate with clinical parameters.
Flow cytometry and single-cell multiomics will be used to characterize TSA-T cells phenotype.
Time frame: After TSA-T cell manufacturing up to infusion of TSA-T cells (up to 24 weeks)
To characterize specificity of manufactured TSA-T cells prior to infusion and correlate with clinical parameters
ELISpot will test the specificity of TSA-T cells to targeted antigens
Time frame: After TSA-T cell manufacturing up to infusion of TSA-T cells (up to 24 weeks)
Plan to share: No
No publications or documents are linked to this record.
Started Sep 2024 (actual). Primary completion is estimated for Dec 2030, 75 months after the start.
Of 41 non-industry phase 1 interventional studies under Medulloblastoma, half reached primary completion within 65 months of starting (the median), counting those still running; a quarter within 44 and three quarters within 88. This study's planned 75 months is above that.
Counting every sponsor, half of 46 studies reached it within 65 months; a quarter within 44 and three quarters within 92.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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