IL-15 and IL-21–armored GPC3-CAR T cell therapy for adults with GPC3-positive solid tumors

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

Researchers collect a small amount of a participant's blood to grow T cells, then use a retrovirus to insert a GPC3-specific chimeric antigen receptor plus IL-15 and IL-21 genes into those cells. Patients receive short lymphodepleting chemotherapy with cyclophosphamide and fludarabine to make room for the infused cells, and the engineered CAR T cells are infused 48–72 hours after chemotherapy. This is a Phase 1 dose-escalation protocol designed to test safety and identify an appropriate dose, with laboratory testing of the manufactured cells before infusion. The trial is conducted at Baylor College of Medicine/Houston Methodist Hospital and enrolls adults with tumors that show GPC3 expression by immunohistochemistry.

Why it matters

Who can join: the full rules

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%
* Life expectancy ≥16 weeks
* Barcelona Clinic Liver Cancer Stage A, B or C (- 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 \* GPC3 expression will be evaluated by standard immunohistochemistry (IHC) at Texas Patients'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:

* Diagnosis of GPC3-positive solid tumor
* Age ≥ 21 years
* Barcelona Clinic Liver Cancer Stage A, B or C
* Life expectancy of ≥ 12 weeks
* Lansky or Karnofsky score ≥ 60%
* Child-Pugh-Turcotte score \< 7
* 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 24hrs 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)

Where it's running

• Houston Methodist Hospital
  Houston, Texas, United States Recruiting

Study contacts

• Principal investigator: Premal Lulla, MD — Baylor College of Medicine
• Study coordinator: Premal Lulla, MD
• Email: lulla@bcm.edu
• Phone: (713) 441-1450

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• CAR-T Therapy Safety, Response, and Immune-Escape: Observational Study in Adults

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.