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Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05103631
Recruitment Status : Recruiting
First Posted : November 2, 2021
Last Update Posted : January 14, 2022
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Houston Methodist Hospital, TX
Information provided by (Responsible Party):
Tannaz Armaghany, Baylor College of Medicine

Brief Summary:

Patients may be considered if the cancer has come back, has not gone away after standard treatment or the patient cannot receive standard treatment. This research study uses special immune system cells called CATCH 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 we can put a new gene (a tiny part of what makes-up DNA and carriesa person's traits) into T cells that will make them recognize cancer cells and kill them . In the lab, we made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33. The antibody GC33 recognizes a protein called GPC3 that is found on the hepatocellular carcinoma the patient has. The specific CAR we are making is called GPC3-CAR. To make this CAR more effective, we also added a gene encoding protein called IL15. This protein helps CAR T cells grow better and stay in the blood longer so that they may kill tumors better. The mixture of GPC3-CAR and IL15 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL 15. This study will test T cells that we have made with CATCH T cells in patients with GPC3-positive hepatocellular carcinoma such as the ones participating in this study.

T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The investigators will insert the iCasp9 and IL15 together into the T cells using a virus that has been made for this study. The drug (AP1903) is an experimental drug that has been tested in humans with no bad side-effects. The investigators will use this drug to kill the T cells if necessary due to side effects.

This study will test T cells genetically engineered with a GPC3-CAR and IL15 (CATCH T cells) in patients with GPC3-positive solid tumors.

The CATCH 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 CATCH 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 CATCH T cells will help people with GPC3-positive hepatocellular carcinoma.


Condition or disease Intervention/treatment Phase
Liver Cell Carcinoma Genetic: CATCH T cells Drug: Cytoxan Drug: Fludara Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Interleukin-15 Armored Glypican-3-specific Chimeric Antigen Receptor Expressing Autologous T Cells as Immunotherapy for Patients With Hepatocellular Carcinoma
Actual Study Start Date : June 17, 2021
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : December 2039

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CATCH T cells + Fludarabine and Cytoxan
GPC3-CAR and the IL15 (CATCH T cells) along with lymphodepleting chemotherapy (Cytoxan and Fludarabine) will be administered to patients with GPC3-positive solid tumors.
Genetic: CATCH T cells

Four 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: 3x10^7/m2

DL2: 1x10^8/m2

DL3: 3x10^8/m2

DL4: 1x10^9/m2

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: Fludara
Fludarabine will be given at a dose of 30 mg/m2/day for 3 days given intravenously.
Other Name: Fludarabine




Primary Outcome Measures :
  1. Number of Patients with Dose Limiting Toxicity [ Time Frame: 4 weeks ]
    A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3-CAR T cells. Specifically those which are Grade 5; non-hematologic Grade 3-4 not returning to Grade 2 within 72 hours; Grade 2-4 allergic reaction; Hematologic Grade 4 that fails to return to Grade 2 or baseline (whichever is more severe) within 14 days; all grade 4 CRS and neurologic toxicities and grade 3 CRS and neurologic toxicities that fail to return to Grade 1 within 7 days.


Secondary Outcome Measures :
  1. Percent of Patients with best response as either complete remission or partial remission [ Time Frame: 4 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 ]
    T cell persistence will be 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:

  • Relapsed or refractory GPC3-positive* hepatocellular carcinomas (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 ≥18 years
  • Lansky or Karnofsky score ≥60%
  • Life expectancy ≥16 weeks
  • Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only)
  • 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

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 Eligibility

Inclusion Criteria:

  • Age ≥ 18 years
  • Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only)
  • Life expectancy of ≥ 12 weeks
  • Lansky or Karnofsky score ≥ 60%
  • Child-Pugh-Turcotte score < 7 (for patients with hepatocellular carcinoma only)
  • Adequate organ function:

    • Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
    • serum AST< 5 times ULN
    • 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
  • 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

Exclusion Criteria:

  • Pregnancy or lactation
  • Uncontrolled infection
  • Systemic steroid treatment (≥ 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)

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): NCT05103631


Contacts
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Contact: Tannaz Armaghany, MD 713-798-3750 Tannaz.Armaghany@bcm.edu
Contact: Ramy Sweidan 832-824-4234 rxsweida@texaschildrens.org

Locations
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United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Tannaz Armaghany    713-798-3750    Tannaz.Armaghany@bcm.edu   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Houston Methodist Hospital, TX
Investigators
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Principal Investigator: Tannaz Armaghany, MD Baylor College of Medicine
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Responsible Party: Tannaz Armaghany, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT05103631    
Other Study ID Numbers: H-49796 CATCH
First Posted: November 2, 2021    Key Record Dates
Last Update Posted: January 14, 2022
Last Verified: January 2022

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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 Tannaz Armaghany, Baylor College of Medicine:
15.GPC3-CAR T cells
GPC3
Glypican
Liver cancer
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
Fludarabine phosphate
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