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

Launched by ST. JUDE CHILDREN'S RESEARCH HOSPITAL · May 18, 2021

Keywords

ClinConnect Summary

The 3CAR trial is a research study looking at a new type of treatment called immunotherapy for children and young adults (up to 21 years old) with specific types of solid tumors, such as neuroblastoma and osteosarcoma. This treatment involves using the patient’s own immune cells, called T cells, which are modified in a lab to better target and fight their cancer. The main goal of the trial is to find out if this treatment is safe and to determine the highest dose that can be given without causing serious side effects. Additionally, the study will look at how well the treatment works against the tumors.

To be eligible for this trial, participants must have a measurable B7-H3-positive solid tumor that has not responded to previous treatments. They also need to be in relatively good health, with a life expectancy of more than 8 weeks, and meet certain health criteria, such as having enough functioning organs. If a patient joins the trial, they can expect to receive an infusion of their modified T cells after going through a preparatory treatment to help their immune system. It’s important to know that the study is currently recruiting participants, and there will be careful monitoring throughout the treatment process to assess safety and effectiveness.

Gender

ALL

Eligibility 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)