Glypican 3-specific Chimeric Antigen Receptor Expressing T Cells for Hepatocellular Carcinoma (GLYCAR)

NCT02905188 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: H-38942 GLYCAR
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study enrolls patients who have a type of cancer that arises from the liver called hepatocellular carcinoma. The cancer has come back, has not gone away after standard treatment, has spread outside of the liver or the patient cannot receive standard treatment. This research study uses special immune system cells called GLYCAR T cells, a new experimental treatment. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. In preclinical studies, the investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33 that recognizes glypican-3, a protein found on almost all hepatocellular carcinoma cells (GPC3-CAR). This study will test T cells genetically engineered with a GPC3-CAR (GLYCAR T cells) in patients with hepatocellular carcinoma. The GLYCAR T cells are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to find the biggest dose of GLYCAR T cells that is safe, to see how long they last in the body, to learn what the side effects are and to see if the GLYCAR T cells will help people with GPC3-positive hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; GPC3-CAR T cells; GPC3-positive hepatocellular carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Patients with Dose Limiting Toxicity

  DLT will be defined as any of the following that may, after consultation with the FDA, be considered possibly, probably, or definitely related to the study cellular products. * Any Grade 5 event * Non-hematologic dose-limiting toxicity is any Grade 3 or Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours * Grade 2 to 4 allergic reaction to CAR T cell infusion. * Hematologic dose limiting toxicity is defined as any Grade 4 hematologic toxicity that fails to return to Grade 2 or baseline (whichever is more severe) within 14 days. * Grade 3 and 4 expected reactions due to CRS and neurotoxicity are seen with the use of CAR-based immunotherapy. Grade 3 cytokine release syndrome (CRS) infusion reactions and neurologic toxicity will only be reported to the FDA if they fail to return to Grade 1 within 7 days. Grade 4 CRS and neurologic toxicities will be reported to the FDA in an expedited fashion.

  6 weeks

• Recommended Phase 2 Dose (RP2D)

  The RP2D is based upon the review of all available data including safety, preliminary anti-tumor activity, and MTD.

  2 years

Secondary Outcomes (2)

• Percent of Patients with best response as either complete remission or partial remission

  6 weeks

• Median T cell persistence

  15 years

Study Arms (1)

GLYCAR T cells + Fludarabine and Cytoxan

EXPERIMENTAL

GPC3-CAR (GLYCAR T cells) along with lymphodepleting chemotherapy (Cytoxan and Fludarabine) will be administered to patients with hepatocellular carcinoma.

Genetic: GLYCAR T cells; Drug: Cytoxan; Drug: Fludarabine

Interventions

GLYCAR T cells GENETIC

Five different dosing schedules will be evaluated. Three to six patients will be evaluated on each dosing schedule. The following dose levels will be evaluated: DL1: 1x10\^7/m2 DL2: 3x10\^7/m2 DL3: 1x10\^8/m2 DL4: 3x10\^8/m2 DL5: 1x10\^9/m2 If DLTs are observed on DL1, patients will be enrolled on DL0 at 3x10\^6/m2 dose. The first patient on each dose level has to be 14 days post T-cell infusion before the second patient can be enrolled. The doses are calculated according to the actual number of GPC3-CAR transduced T cells.

Also known as: GPC3-CAR T cells

GLYCAR T cells + Fludarabine and Cytoxan

Cytoxan DRUG

Cyclophosphamide will be given at a dose of 500 mg/m2/day for 3 days given intravenously

Also known as: Cyclophosphamide

GLYCAR T cells + Fludarabine and Cytoxan

Fludarabine DRUG

Fludarabine will be given at a dose of 30 mg/m2/day for 3 days given intravenously

GLYCAR T cells + Fludarabine and Cytoxan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histology-proven hepatocellular carcinoma (HCC) which is unresectable, recurrent and/or metastatic
• Barcelona Clinic Liver Cancer Stage A, B or C
• GPC3-positive HCC
• Age ≥ 18 years
• Karnofsky score ≥ 60% (See appendix I)
• Life expectancy ≥ 12 weeks
• Child-Pugh-Turcotte score \<8
• Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

You may not qualify if:

• 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 liver transplantation
• Known HIV positivity
• Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)
• Severe previous toxicity from cyclophosphamide or fludarabine
• Treatment Eligibility
• Histology-proven hepatocellular carcinoma (HCC) which is unresectable, recurrent and/or metastatic
• Barcelona Clinic Liver Cancer Stage A, B or C
• GPC3-positive HCC
• Age ≥ 18 years
• Life expectancy of ≥ 12 weeks
• Karnofsky score ≥ 60%
• Child-Pugh-Turcotte score \< 8
• Adequate organ function:
• creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 ml/min

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator
• Cancer Prevention Research Institute of Texas: collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Tannaz Armaghany, M.D.

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 14, 2016
• First Posted: September 19, 2016
• Study Start: March 28, 2019
• Primary Completion: November 17, 2021
• Study Completion: January 6, 2023
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)