Using engineered T cells to treat pediatric solid tumors
Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressing Autologous T Cells as an Immunotherapy for Children With Solid Tumors (CARE)
This study is testing a new treatment using specially modified immune cells to see if they can help children with certain types of solid tumors, like liver cancer and rhabdomyosarcoma, feel better.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 1 Year to 21 Years |
| Sex | All |
| Sponsor | Baylor College of Medicine Academic / other |
| Drugs / interventions | CAR T, chemotherapy, prednisone, chimeric antigen receptor, cyclophosphamide, fludarabine, Cytoxan |
| Locations | 1 site (Houston, Texas) |
| Trial ID | NCT04715191 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates a novel treatment for pediatric patients with GPC3-positive solid tumors, including liver cancer and rhabdomyosarcoma, by utilizing genetically modified T cells known as CAR T cells. The study involves collecting blood from participants to grow these T cells, which are then engineered to target and kill cancer cells. Prior to the infusion of these CAR T cells, participants will undergo lymphodepletion chemotherapy to enhance the effectiveness of the treatment. The trial aims to assess the safety and efficacy of this approach in a small group of patients.
Who should consider this trial
Good fit: Ideal candidates are pediatric patients aged 1 to 21 years with GPC3-positive solid tumors who have not responded to standard treatments.
Not a fit: Patients with a history of hypersensitivity to murine proteins or those with active infections may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for children with difficult-to-treat solid tumors.
How similar studies have performed: Previous studies using CAR T cell therapies have shown promise in treating various cancers, suggesting potential success for this novel approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Procurement Eligibility Inclusion Criteria: * Diagnosis of GPC3-positive\* solid tumors (as determined by immunohistochemistry with an extent score of \>=Grade 2 \[\>25% positive tumor cells\] and an intensity score of \>= 2 \[scale 0-4\]). * Age ≥1 year and ≤ 21 years * Lansky or Karnofsky score ≥60% * Life expectancy ≥16 weeks * Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only) * Child-Pugh-Turcotte score \<7 (for patients with hepatocellular carcinoma only) * Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent Exclusion Criteria: * History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies). * History of organ transplantation * Known HIV positivity * Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections) Treatment Eligibility Inclusion Criteria: * Age ≥ 1 year and ≤ 21 years * Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only) * Lansky or Karnofsky score ≥ 60% * Child-Pugh-Turcotte score \< 7 (for patients with hepatocellular carcinoma only) * Adequate organ function: * Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min * Total bilirubin \< 3 times ULN for age * INR ≤1.7 (for patients with hepatocellular carcinoma only) * Absolute neutrophil count \> 750/µl * Platelet count \> 75,000/µl (Needs to be confirmed prior to treatment whether with or without transfusion) * Hgb ≥ 8.0 g/dl (Needs to be confirmed prior to treatment whether with or without transfusion) * Pulse oximetry ≥ 92% on room air * Incurable disease after treatment with up- front therapy (Patients who have relapsed disease despite a standard of care salvage therapy) * Wash out period, such that patient has recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study, and returned to their clinical baseline, as determined by history and physical exam. * Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the T-cell infusion. * Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent Exclusion Criteria: * Pregnancy or lactation * Uncontrolled infection * Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day, dose adjustment or discontinuation of medication must occur at least 24 hours prior to CAR T cell infusion) * Known HIV positivity * Active bacterial, fungal or viral infection \[except Hepatitis B (HBV patients with active disease who meet the criteria for anti-HBV therapy should be on a suppressive antiviral therapy prior to initiation of cancer therapy) or Hepatitis C virus infections (should have completed curative antiviral treatment with HCV viral load below the limit of quantification\] * Congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis * Active autoimmune or inflammatory disorder * Live vaccines within 30 days prior to enrollment * History of organ transplantation * History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
Where this trial is running
Houston, Texas
- Texas Children's Hospital — Houston, Texas, United States (Recruiting)
Study contacts
- Principal investigator: David Steffin, MD — Baylor College of Medicine
- Study coordinator: David Steffin
- Email: dhsteffi@texaschildrens.org
- Phone: (832) 824-4233
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.