This clinical study will test the effect of 21.15.GPC3-CAR T cells in patients with solid tumors including Hepatoblastoma, Hepatocellular Carcinoma, Wilms Tumor, Malignant Rhabdoid Tumor, Yolk Sac Tumor, Rhabdomyosarcoma, Liposarcoma and Embryonal Sarcoma of Liver that express a molecule called GPC3 on their surface.
The strategy was developed at Texas Children’s / Baylor College of Medicine and is based on the innate properties of special white blood cells called T cells, which can be redirected to recognize and kill cancer cells. In this study, the T cells are genetically engineered to express three different molecules:
the GPC3-CAR which helps them identify cancer cells, activate the T cells to kill the cancer cells and signal to the T cells to grow and proliferate.
Interleukiin-15 and -21 which are soluble molecules that can help the T cells survive and grow better.
In addition, the cells are engineered to contain a safety switch which can be activated with a small intravenous injection to eliminate overactive CAR T cells in case of unwanted toxicities, thereby maximizing the safety profile of this therapeutic approach. The 21.15.GPC3-CAR T cells are an investigational product not yet approved by the Food and Drug Administration.
Description
This is a single arm study that will evaluate the safety of 21.15.GPC3-CAR T cells in patients with GPC3-positive solid tumors. In addition, the team will study how these CAR T cells expand in patients and whether they can induce the tumor to shrink or completely disappear.
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 ≥21 years
Lansky or Karnofsky score ≥60% (See Appendix I)
Life expectancy ≥16 weeks
Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only, See Appendix II)
Child-Pugh-Turcotte score <7 (for patients with hepatocellular carcinoma only, See Appendix III)
Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent *
GPC3 expression will be evaluated by standard immunohistochemistry (IHC) at Texas Children's Hospital/Baylor College of Medicine, Department of Pathology for all patients to meet procurement eligibility. All patients will send at least 5 unstained slides.
Procurement 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 Inclusion Criteria
Age ≥ 21 years
Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only, See Appendix II)
Life expectancy of ≥ 12 weeks
Lansky or Karnofsky score ≥ 60% (See Appendix I)
Child-Pugh-Turcotte score < 7 (for patients with hepatocellular carcinoma only, See Appendix III)
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 > 500/µl
platelet count > 25,000/µl (can be transfused)
Hgb ≥ 7.0 g/dl (can be transfused)
Pulse oximetry >90% on room air
Refractory or relapsed disease after treatment with up- front therapy and at least one salvage treatment cycle
Recovered from acute toxic effects of all prior chemotherapy and investigational agents before entering this study, as determined by history and physical exam
Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.
Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
Treatment 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 or Hepatitis C virus infections)
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)
Detailed inclusion and exclusion criteria as listed on clinicaltrials.gov