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Trial record 22 of 258 for:    "methodist hospital" | Recruiting, Not yet recruiting, Available Studies | Houston

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

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ClinicalTrials.gov Identifier: NCT02905188
Recruitment Status : Not yet recruiting
First Posted : September 19, 2016
Last Update Posted : June 8, 2018
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Information provided by (Responsible Party):
Andras Heczey, Baylor College of Medicine

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.


Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Genetic: GLYCAR T cells Drug: Cytoxan Drug: Fludarabine Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Glypican 3-specific Chimeric Antigen Receptor Expressing T Cells as Immunotherapy for Patients With Hepatocellular Carcinoma
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : October 2036

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GLYCAR T cells + Fludarabine and Cytoxan
GPC3-CAR (GLYCAR T cells) along with lymphodepleting chemotherapy (Cytoxan and Fludarabine) will be administered to patients with hepatocellular carcinoma.
Genetic: GLYCAR T cells

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.

Other Name: GPC3-CAR T cells

Drug: Cytoxan
Cyclophosphamide will be given at a dose of 500 mg/m2/day for 3 days given intravenously
Other Name: Cyclophosphamide

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




Primary Outcome Measures :
  1. Number of Patients with Dose Limiting Toxicity [ Time Frame: 6 weeks ]

    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.


Secondary Outcome Measures :
  1. Percent of Patients with best response as either complete remission or partial remission [ Time Frame: 6 weeks ]
    Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the two patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.

  2. Median T cell persistence [ Time Frame: 15 years ]
    as measured by PCR



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Procurement Eligibility

Inclusion Criteria:

  • 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 <7
  • 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 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

Inclusion Criteria:

  • 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 < 7
  • Adequate organ function:

    • creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 ml/min
    • serum AST< 5 times ULN
    • total bilirubin < 3 times ULN for age
    • INR ≤1.7
    • absolute neutrophil count > 500/microliter
    • platelet count > 20,000/microliter (can be transfused)
    • Hgb ≥9.0 g/dl (can be transfused)
    • Pulse oximetry >90% on room air
  • Recovered from acute toxic effects of all prior chemotherapy before entering this study
  • Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion.
  • Available autologous transduced T cells with greater than or equal to 20% expression of GPC3 CAR determined by flow-cytometry and killing of GPC3-positive targets greater than or equal to 20% in cytotoxicity assay
  • Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria:

  • Eligible for complete tumor resection, liver transplantation, transarterial chemoembolization (TACE), Y-90 treatment or Radiofrequency ablation (RFA).
  • Pregnancy or lactation (for women at child-bearing age, birth control is required)
  • Receiving investigational drugs within 2 weeks prior to treatment
  • Hepatic encephalopathy
  • Uncontrolled infection
  • Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
  • Known HIV positivity
  • Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)
  • History of liver transplantation
  • Heart failure of Class II-IV and / or B-D per NYHA 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)
  • Severe previous toxicity from cyclophosphamide or fludarabine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02905188


Contacts
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Contact: Andras A Heczey, M.D. 832-824-4233 axheczey@txch.org

Locations
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United States, Texas
Houston Methodist Hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: Andras Heczey, MD       axheczey@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Investigators
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Principal Investigator: Andras A Heczey, M.D. Baylor College of Medicine

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Responsible Party: Andras Heczey, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02905188     History of Changes
Other Study ID Numbers: H-38942 GLYCAR
First Posted: September 19, 2016    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Andras Heczey, Baylor College of Medicine:
hepatocellular carcinoma
GPC3-CAR T cells
GPC3-positive hepatocellular carcinoma

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents