Texas Children's Cancer and Hematology Center Immunotherapy For Children With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells (CARE)

Diseases and Description

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.

• The following dose levels will be evaluated:
  • DL0: 3x10^7/m2 DL1: 1x10^8/m2 DL2: 3x10^8/m2 DL3: 1x10^9/m2

Eligibility

Procurement 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 ≥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