B7-H3 CAR T-cell therapy for pediatric solid tumors
B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)
This study is testing a new type of immune therapy using specially modified T cells to see if it can help children with tough-to-treat solid tumors.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 48 (estimated) |
| Ages | N/A to 21 Years |
| Sex | All |
| Sponsor | St. Jude Children's Research Hospital Academic / other |
| Drugs / interventions | CAR T, chemotherapy, immunotherapy |
| Locations | 1 site (Memphis, Tennessee) |
| Trial ID | NCT04897321 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the use of genetically engineered T cells that target the B7-H3 protein in pediatric patients with relapsed or refractory solid tumors. It is a Phase I trial that aims to determine the safety and maximum tolerated dose of these B7-H3-CAR T cells following lymphodepleting chemotherapy. The study will also evaluate the antitumor activity of the treatment and assess changes in the tumor environment post-infusion. Participants will receive a single infusion of the CAR T cells, and the study will last for one year, including a follow-up period.
Who should consider this trial
Good fit: Ideal candidates are pediatric patients aged 21 years or younger with measurable B7-H3-positive solid tumors.
Not a fit: Patients with primary immunodeficiencies or severe infections may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could provide a new treatment option for children with difficult-to-treat solid tumors.
How similar studies have performed: Other studies using CAR T-cell therapy have shown promising results, indicating potential success for this approach in treating solid tumors.
Eligibility criteria
Show full inclusion / exclusion 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)
Where this trial is running
Memphis, Tennessee
- St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)
Study contacts
- Principal investigator: Chris DeRenzo, MD — St. Jude Children's Research Hospital
- Study coordinator: Chris DeRenzo, MD
- Email: referralinfo@stjude.org
- Phone: 866-278-5833
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.