B7-H3.CD28Z.CART in CNS Neoplasms
A Phase 1/1b Study of Autologous b7-h3 Chimeric Antigen Receptor t Cells (b7-h3.cd28z.Cart) in Children and Young Adults With Recurrent or Progressive Cns Neoplasms Expressing b7-h3 Target
1 other identifier
interventional
70
1 country
2
Brief Summary
The purpose of this research study is to test the safety and effectiveness of a cell therapy at different doses for children and young adults with recurrent or progressive brain tumors. Recurrent/recurred means a tumor that has gone away and then came back. This cell therapy is called B7- H3.CD28Z.CART, referred to as B7-H3 CAR T cells. B7-H3 is a protein that is over-expressed on many tumor cells, making it a good target for cancer cell therapy. The names of the study investigational therapies involved in this study are:
- Fludarabine (a type of chemotherapy)
- Cyclophosphamide (a type of chemotherapy)
- B7-H3 CAR T cells (a type of cellular therapy)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2026
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 28, 2026
CompletedFirst Posted
Study publicly available on registry
February 5, 2026
CompletedStudy Start
First participant enrolled
July 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2030
Study Completion
Last participant's last visit for all outcomes
August 31, 2032
February 5, 2026
January 1, 2026
4.2 years
January 28, 2026
January 28, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Manufacturing Success Rate of Autologous B7-H3.CD28Z CAR T Cells
Each participant's product will be tested for the following criteria: cell viability ≥ 70%; cell number within ± 20% of the planned dose; CD3+ T cells ≥ 80% of leukocytes; CAR-positive cells ≥ 10% of CD3+ T cells; endotoxin ≤ 5 EU/kg; mycoplasma not detected; vector copy number (VCN) per transduced cell ≤ 10; replication-competent retrovirus (RCR) not detected; and sterility confirmed as "No Growth to Date" (NGTD) after a minimum of 5 days in culture. A participant will be classified as a manufacturing success if the final product satisfies all release criteria. If any criterion is not met, the participant will be classified as a manufacturing failure. The manufacturing success rate is defined as the proportion of participants classified as a success.
Participants will receive the CART cell infusion on Day 0.
Maximum Tolerated Dose (MTD) of B7-H3.CD28Z.CART Cells
The MTD is defined as the highest dose level of B7-H3.CD28Z.CART cells at which the rate of dose-limiting toxicity (DLT) is considered acceptable according to the modified 3+3 rules. Additional details are provided in Protocol Section 13.1. Definition of DLT is outlined in protocol. The definition of DLT uses NCI's Common Terminology Criteria for Adverse Events (CTCAEv6.0).
28 days
Recommended Phase 2 Dose (RP2D) of B7-H3.CD28Z.CART Cells
The recommended phase 2 dose (RP2D) is the dose of B7-H3.CD28Z.CAR T cells selected for Phase 2 based on Phase 1 results, considering safety, tolerability, manufacturing feasibility, and observed clinical activity, and may be at or below the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD).
28 days
Secondary Outcomes (14)
Number of Participants Experience Dose-Limiting Toxicity (DLT) during Dose Escalation
28 years
Number of Participants Experience Dose-Limiting Toxicity (DLT) at Maximum Tolerated Dose (MTD) / Recommend Phase 2 Dose (RP2D)
28 days
Number of Participants with Two Additional ICV B7-H3.CD28Z.CAR T Infusions
From Day 0 (initial IV infusion) through Day 56 (third ICV infusion)
Adverse Events of Special Interest (AESIs) Rate
From Day 0 (initial IV infusion) through Day 56 (third ICV infusion) plus a 28-day follow-up period, for a total of 74 days.
Complete Response Rate (CRR) at Day 28
Day 28
- +9 more secondary outcomes
Study Arms (4)
Dose Escalation for B7-H3.CD28Z.CART in Standard Risk Stratum
EXPERIMENTALParticipants will be enrolled in a staggered, sequential fashion using a modified 3 + 3 dose escalation design, assigning participants to one of three intravenous dose levels to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of IV B7-H3.CD28Z.CART. Dose escalation will occur per dose-limiting toxicity rules. * Baseline visit * Apheresis to obtain T cells * Days -4, -3, -2: predetermined doses of Fludarabine and Cyclophosphamide 1x daily * Day 0: B7-H3 CAR T cell infusion 1x daily * 2 doses of B7-H3 CAR T cell infusion Intracerebroventricular (ICV) Infusion every 28 days until 8 doses total according to clinical response * Follow up every 3 months after last infusion up until 2 years * Long term follow annually for an additional 13 years
Dose Escalation for B7-H3.CD28Z.CART in High Risk Stratum
EXPERIMENTALParticipants will be enrolled in a staggered, sequential fashion using a modified 3 + 3 dose escalation design, assigning participants to one of three intravenous dose levels to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of IV B7-H3.CD28Z.CART. Dose escalation will occur per dose-limiting toxicity rules. * Baseline visit * Apheresis to obtain T cells * Days -4, -3, -2: predetermined doses of Fludarabine and Cyclophosphamide 1x daily * Day 0: B7-H3 CAR T cell infusion 1x daily * 2 doses of B7-H3 CAR T cell infusion Intracerebroventricular (ICV) Infusion every 28 days until 8 doses total according to clinical response * Follow up every 3 months after last infusion up until 2 years * Long term follow annually for an additional 13 years
Dose Expansion for B7-H3.CD28Z.CART in Standard Risk Stratum
EXPERIMENTALDose expansion will occur per dose-limiting toxicity rules. * Baseline visit * Apheresis to obtain T cells * Days -4, -3, -2: predetermined doses of Fludarabine and Cyclophosphamide 1x daily * Day 0: B7-H3 CAR T cell infusion 1x daily * 2 doses of B7-H3 CAR T cell infusion Intracerebroventricular (ICV) Infusion every 28 days until 8 doses total according to clinical response * Follow up every 3 months after last infusion up until 2 years * Long term follow annually for an additional 13 years
Dose Expansion for B7-H3.CD28Z.CART in High Risk Stratum
EXPERIMENTALDose expansion will occur per dose-limiting toxicity rules. * Baseline visit * Apheresis to obtain T cells * Days -4, -3, -2: predetermined doses of Fludarabine and Cyclophosphamide 1x daily * Day 0: B7-H3 CAR T cell infusion 1x daily * 2 doses of B7-H3 CAR T cell infusion Intracerebroventricular (ICV) Infusion every 28 days until 8 doses total according to clinical response * Follow up every 3 months after last infusion up until 2 years * Long term follow annually for an additional 13 years
Interventions
Autologous CAR T cells targeting B7-H3 (CD276), administered intravenously (into the vein) per protocol.
Lymphodepleting chemotherapy administered intravenously per institutional standards.
Lymphodepleting chemotherapy administered intravenously per institutional standards.
Eligibility Criteria
You may qualify if:
- Participants must have histologically and/or molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent/progressive following standard of care treatment.
- Eligible CNS embryonal tumor types include:
- Medulloblastoma
- Atypical Teratoid Rhabdoid Tumor (ATRT)
- Embryonal Tumor with Multilayered Rosettes (ETMR) Pineoblastoma
- Other CNS embryonal tumor types, at the discretion of the study chair (or designee)
- Participants must have adequate pre-trial tumor material available to determine B7- H3 expression status. Tumor tissue from the most recent resection or biopsy of recurrent disease is preferred. If unavailable, tumor tissue from prior recurrences or from time of initial diagnosis is acceptable. Biopsies will not be performed for participation in this research trial or for research purposes.
- Pre-screening IHC Consent: All participants ≥ 18 years of age must be able to give informed consent. For participants \<18 years of age, their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric participants will be included in age-appropriate discussion and written assent will be obtained for those ≥10 years of age, where appropriate. If a minor becomes of age during participation of this study, they will be asked to reconsent as an adult.
- Participants must have histologically and/or molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent/progressive following standard of care treatment.
- Eligible CNS embryonal tumor types include:
- Medulloblastoma
- Atypical Teratoid Rhabdoid Tumor (ATRT)
- Embryonal Tumor with Multilayered Rosettes (ETMR)
- Pineoblastoma
- Other CNS embryonal tumor types, at the discretion of the study chair (or designee)
- +53 more criteria
You may not qualify if:
- Participants with bulky tumor are ineligible. Bulky tumor is defined as:
- Tumor with diameter of \>5cm in one dimension on T2/FLAIR sequence
- Tumor with evidence of clinically significant midline shift or uncal herniation
- Tumor that, in opinion of the site investigator, shows significant mass effect in either the brain or spine
- Participants with clinical or radiological evidence of brain herniation.
- Participants who have received other B7-H3 targeted cellular therapies. Other prior cellular therapies are eligible, including immune checkpoint inhibition and vaccine therapy. These prior therapies should be discussed with the study chair (or designee) prior to participant enrollment.
- Concurrent illness
- Participants with any prior immunodeficiency or history of autoimmune disease requiring systemic steroids/ immunosuppressive medication/ disease-modifying agents within the last two (2) years.
- Uncontrolled (Grade 3) bacterial, viral, fungal, or other infection.
- Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
- Evidence of severe or uncontrolled systemic disease (e.g. Grade 3 significant cardiac, pulmonary, hepatic, renal or other organ dysfunction) that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.
- Known sensitivity or allergy to any of the agents/reagents used in this study (i.e. DSMO, cyclophosphamide, fludarabine)
- History of severe hypersensitivity reaction to compounds of similar chemical or biologic compositions to any agent used in the study or in the manufacturing of cells.
- Concomitant medications
- Current systemic corticosteroid therapy
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Robbie Majznerlead
- National Institutes of Health (NIH)collaborator
Study Sites (2)
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Susan Chi
Dana-Farber Cancer Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Sponsor-Investigator
Study Record Dates
First Submitted
January 28, 2026
First Posted
February 5, 2026
Study Start (Estimated)
July 1, 2026
Primary Completion (Estimated)
August 31, 2030
Study Completion (Estimated)
August 31, 2032
Last Updated
February 5, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.