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

• Status: Not yet recruiting
• Trial end date: 2027-03-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital
• Treatments: Cyclophosphamide; Fludarabine

Criteria

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)