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3CAR is a Phase 1 immunotherapy trial evaluating autologous T cells genetically engineered to express B7-H3-targeted chimeric antigen receptors in patients aged 21 or younger with relapsed/refractory B7-H3-positive solid tumors. The primary objective is to determine the safety and maximum tolerated dose of a single intravenous infusion of B7-H3-CAR T cells after lymphodepleting chemotherapy, with antitumor activity as a secondary objective. Study interventions include fludarabine (Fludara), cyclophosphamide (Cytoxan) and MESNA (Mesnex); eligibility requires measurable B7-H3-positive disease confirmed by standard immunohistochemistry.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
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)