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RecruitingInterventionalPhase 1

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

NCT ID: NCT04897321Sponsor: St. Jude Children's Research HospitalLast updated: 2026-05-19

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

Detailed description

Treatment will include a single infusion of B7-H3-CAR T cells after lymphodepleting chemotherapy, with dosing based on the number of CAR+ T cells and patient weight. The study will evaluate the safety and maximum tolerated dose (MTD) of B7-H3-CAR T cells, using a standard 3+3 study design and a 6-week evaluation period. The total study duration will be 1 year, at which point patients will enroll on our existing institutional long-term follow-up protocol.

Arms & interventions

  • DrugFludarabine

    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

  • DrugCyclophosphamide

    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

  • DrugMESNA

    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

  • DrugB7-H3 CAR T cells

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

Outcome measures

Primary

  • Safety of B7-H3-CAR T cells

    A phase I design to determine the maximum tolerated dose (MTD) of autologous, B7-H3-CAR T cells. Four dose levels (3x10\^5/kg, 1x10\^6/kg, 3x10\^6/kg, and 1x10\^7/kg) will be evaluated.

    Time frame: 6 weeks after B7-H3-CAR T cell infusion

Secondary

  • Clinical Response

    Time frame: 6 weeks after B7-H3-CAR T cell infusion

Eligibility criteria

Sex: AllAge: Up to 21 YearsHealthy volunteers: No
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 locations (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105

Recruiting
Chris DeRenzo, MD · Contact
Chris DeRenzo, MD · Principal Investigator