Recruiting

Phase 1

B7-H3-Specific CAR T-Cell TherapyB7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Sponsor:

St. Jude Children's Research Hospital

Code:

NCT04897321

Conditions

Pediatric Solid Tumor

Osteosarcoma

Rhabdomyosarcoma

Neuroblastoma

Ewing Sarcoma

Eligibility Criteria

Sex: All

Age: 0 - 21

Healthy Volunteers: Not accepted

Interventions

Fludarabine

Cyclophosphamide

MESNA

B7-H3 CAR T cells

Study Details

Brief summary:

3CAR is being done to investigate an immunotherapy for patients with solid tumors. It is a Phase I clinical trial evaluating the use of autologous T cells genetically engineered to express B7-H3-CARs for patients ≤ 21 years old, with relapsed/refractory B7-H3+ solid tumors. This study will evaluate the safety and maximum tolerated dose of B7-H3-CAR T cells.The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give to patients with B7-H3-positive solid tumors.

Primary objective

To determine the safety of one intravenous infusion of autologous, B7-H3-CAR T cells in patients (≤ 21 years) with recurrent/refractory B7-H3+ solid tumors after lymphodepleting chemotherapy

Secondary objective

To evaluate the antitumor activity of B7-H3-CAR T cells

Exploratory objectives

To evaluate the tumor environment after treatment with B7-H3-CAR T cells
To assess the immunophenotype, clonal structure and endogenous repertoire of B7-H3-CAR T cells and unmodified T cells
To characterize the cytokine profile in the peripheral blood after treatment with B7-H3-CAR T cells

Conditions

Pediatric Solid Tumor

Osteosarcoma

Rhabdomyosarcoma

Neuroblastoma

Ewing Sarcoma

Study ID

NCT04897321

Start date

Jul 6, 2022

Status verified date

May, 2026

Completion date

Mar 1, 2028

Anticipated

Primary completion date

Mar 1, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 0 - 21

Healthy Volunteers: Not accepted

Inclusion Criteria:

Procurement and T-cell production eligibility\*

\*a previously collected, autologous leukapheresis product can be used for T-cell production

Age ≤21 years old
B7-H3+ solid tumor with measurable disease; B7-H3 expression will be evaluated by standard immunohistochemistry (IHC) using a previously obtained biopsy; a tumor is considered B7-H3 positive with an H-score ≥100
Estimated life expectancy of >12 weeks
Karnofsky or Lansky (age-dependent) performance score ≥50
For females of child bearing age:
Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
Not lactating with intent to breastfeed
Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis

Exclusion Criteria:

Known primary immunodeficiency
Known HIV positivity
Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection)
History of hypersensitivity reactions to murine protein-containing products
Rapidly progressive disease (in the opinion of the study PIs)

Inclusion criteria

Treatment eligibility

Age ≤21 years old
B7-H3+ solid tumor with measurable disease
Evidence of relapsed or refractory disease after standard first-line therapy
Estimated life expectancy of >8 weeks
Karnofsky or Lansky (age-dependent) performance score≥50
Echocardiogram with a ventricular ejection fraction
>40%; or shortening fraction ≥25%
Adequate renal function defined as creatinine clearance or radioisotope GFR 50 ml/min/1.73m2 (GFR 40 ml/min/1.73m2 if < 2 years of age)
Adequate pulmonary function defined as pulse oximetry ≥92% on room air or forced vital capacity (FVC) ≥50% of predicted value
Total Bilirubin ≤3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age
Hemoglobin≥ 7g/dL (can be transfused)
Platelet count >50,000/uL (can be transfused)
Absolute neutrophil count (ANC) ≥ 1000/uL
Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy
For females of child bearing age:
Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
Not lactating with intent to breastfeed
If sexually active, agreement to use birth control until 3 months after T-cell infusion. Male partners should use a condom.
Available autologous transduced T-cell product that has met GMP release criteria
Agreement to participate in long-term follow-up protocol for patients, who have received genetically modified cell products

Exclusion criteria

Known primary immunodeficiency
History of HIV infection
Severe, uncontrolled intercurrent bacterial, viral or fungal infection
History of hypersensitivity reactions to murine protein-containing products
Receiving systemic steroid therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to B7-H3-CAR T-cell infusion
Receiving systemic therapy in the 14 days prior to CAR T-cell infusion, which will interfere with the activity of the B7-H3-CAR product (in the opinion of the study PIs).
Rapidly progressing disease (in the opinion of the study PIs)

Study Design

Enrollment

48 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Treatment Phase

During the treatment phase, the participant receives an infusion of the B7-H3-CAR T cells that were made in the Collection and Manufacturing Phase. Chemotherapy is given for several days prior to the cellular infusion. Patients are then monitored for possible side effects, as well as effects of the treatment on their cancer.

Interventions

Fludarabine

Fludarabine phosphate is a synthetic purine nucleoside analog. It acts by inhibiting DNA polymerase, ribonucleotide reductase and DNA primase by competing with the physiologic substrate, deoxyadenosine triphosphate, resulting in inhibition of DNA synthesis. Intravenous

Cyclophosphamide

Cyclophosphamide is a nitrogen mustard derivative. It acts as an alkylating agent that causes cross-linking of DNA strands by binding with nucleic acids and other intracellular structures, thus interfering with the normal function of DNA. Intravenous

MESNA

Mesna is a synthetic sulfhydryl (thiol) compound. Mesna contains free sulfhydryl groups that interact chemically with urotoxic metabolites of oxaza-phosphorine derivatives such as cyclophosphamide and ifosfamide

B7-H3 CAR T cells

The study participant will receive B7-H3-CAR T cells by vein, through either an IV or a central line.

Primary outcome measure

Safety of B7-H3-CAR T cells [ Time Frame: 6 weeks after B7-H3-CAR T cell infusion ]

Central Contacts and Locations

Central contacts

Chris DeRenzo, MD

888-226-4343 referralinfo@stjude.org

Locations

St. Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Chris DeRenzo, MD

888-226-4343 referralinfo@stjude.org

Principal Investigator:

Chris DeRenzo, MD

More Information

Sponsor

St. Jude Children's Research Hospital

Last update posted

May 19, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by St. Jude Children's Research Hospital on 2026-05-19.