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Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Patients With Pediatric Solid Tumors (GAP) (GAP)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02932956
Recruitment Status : Active, not recruiting
First Posted : October 13, 2016
Last Update Posted : April 19, 2022
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Cancer Prevention Research Institute of Texas
The V Foundation
Cookies for Kids' Cancer
Curing Kids' Cancer Foundation
Information provided by (Responsible Party):
Andras Heczey, Baylor College of Medicine

Brief Summary:

This study enrolls patients who have GPC3-positive solid tumors currently. 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 GAP 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 proteoglycan found on solid tumors including pediatric liver cancers (GPC3-CAR). This study will test T cells genetically engineered with a GPC3-CAR (GAP T cells) in patients with GPC3-positive solid tumors (currently only enrolling liver tumors).

The GAP 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 GAP 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 GAP T cells will help people with GPC3-positive solid tumors. This study enrolls patients who have GPC3-positive solid tumors (currently only enrolling liver tumors).


Condition or disease Intervention/treatment Phase
Liver Cancer Genetic: GAP T cells Drug: Cytoxan Drug: Fludara Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells as Immunotherapy for Patients With Pediatric Solid Tumors
Actual Study Start Date : December 17, 2018
Actual Primary Completion Date : September 27, 2021
Estimated Study Completion Date : February 2037

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

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

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: 6 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: 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:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Procurement Eligibility

Inclusion Criteria:

  • Relapsed or refractory GPC3-positive* solid tumors (currently only enrolling liver tumors)
  • Age ≥ 1 year and ≤ 21 years
  • Lansky or Karnofsky score ≥60%
  • Life expectancy ≥16 weeks
  • 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)
  • Severe previous toxicity from cyclophosphamide or fludarabine

Treatment Eligibility

Inclusion Criteria:

  • Age ≥ 1 year and ≤ 21 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/microliter
    • platelet count > 25,000/microliter (can be transfused)
    • Hgb ≥7.0 g/dl (can be transfused)
    • pulse oximetry >90% on room air
  • 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 (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)
  • Severe previous toxicity from cyclophosphamide or fludarabine

GPC3 expression will be evaluated by standard immunohistochemistry (IHC). A tumor is considered GPC3 positive, when the staining is Grade 2 (>25% positive tumor cells) or above with an intensity score of 2 or above on a scale of 0 to 4.


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): NCT02932956


Locations
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United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Cancer Prevention Research Institute of Texas
The V Foundation
Cookies for Kids' Cancer
Curing Kids' Cancer Foundation
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: NCT02932956    
Other Study ID Numbers: H-39410- GAP
GAP ( Other Identifier: Baylor )
First Posted: October 13, 2016    Key Record Dates
Last Update Posted: April 19, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Andras Heczey, Baylor College of Medicine:
GPC3-CAR T cells
GPC3
Glypican
Liver cancer
Additional relevant MeSH terms:
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Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
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