Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
1 other identifier
interventional
24
1 country
1
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 CARE 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 (a tiny part of what makes-up DNA and carries a person's traits) into T cells that will make them recognize cancer cells and kill them. In the lab, investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GPC3. The antibody GPC3 recognizes a protein found solid tumors including pediatric liver cancers. This CAR is called GPC3-CAR. To make this CAR more effective, investigators also added two genes that includes IL15 and IL21, which are protein that 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 plus IL21 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL15 plus IL21 .This study will test T cells that investigators made (called genetic engineering) with GPC3-CAR and the IL15 plus IL21 (CARE T cells) in patients with GPC3-positive solid tumors. 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 plus IL21 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 plus IL21 (CARE T cells) in patients with GPC3-positive solid tumors. The CARE 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 CARE 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 CARE T cells will help people with GPC3-positive solid tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2024
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 15, 2021
CompletedFirst Posted
Study publicly available on registry
January 20, 2021
CompletedStudy Start
First participant enrolled
May 24, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 3, 2041
May 2, 2025
April 1, 2025
2.2 years
January 15, 2021
April 30, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Patients with Dose Limiting Toxicity
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 7 days 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.
4 weeks
Secondary Outcomes (3)
Percent of Patients with best response as either complete remission or partial remission
4 weeks
Median T cell persistence
15 years
Manufacturing feasibility of 21.15.GBBz T cells
3 years
Study Arms (1)
CARE T cells + Fludarabine and Cytoxan
EXPERIMENTALGPC3-CAR and the IL15 plus IL21 (CARE T cells) along with lymphodepleting chemotherapy (Cytoxan and Fludarabine) will be administered to patients with GPC3-positive solid tumors.
Interventions
Four different dosing schedules will be evaluated. The following dose levels will be evaluated: DL0: 1x10\^7/m\^2 DL1: 3x10\^7/m\^2 DL2: 1x10\^8/m\^2 DL3: 3x10\^8/m\^2 The doses are calculated according to the actual number of GPC3-CAR transduced T cells.
Cyclophosphamide will be given at a dose of 500 mg/m2/day for 3 days given intravenously.
Fludarabine will be given at a dose of 30 mg/m2/day for 3 days given intravenously.
Eligibility Criteria
You may qualify if:
- 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 ≥1 year and ≤ 21 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
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 organ transplantation
- Known HIV positivity
- Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)
- Treatment Eligibility
- Age ≥ 1 year and ≤ 21 years
- Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only)
- 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
- Total bilirubin \< 3 times ULN for age
- INR ≤1.7 (for patients with hepatocellular carcinoma only)
- Absolute neutrophil count \> 750/µl
- Platelet count \> 75,000/µl (Needs to be confirmed prior to treatment whether with or without transfusion)
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Texas Children's Hospital
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andras Heczey, MD
Baylor College of Medicine
- PRINCIPAL INVESTIGATOR
David Steffin, MD
Baylor College of Medicine
Central Study Contacts
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
January 15, 2021
First Posted
January 20, 2021
Study Start
May 24, 2024
Primary Completion (Estimated)
August 1, 2026
Study Completion (Estimated)
July 3, 2041
Last Updated
May 2, 2025
Record last verified: 2025-04
Data Sharing
- IPD Sharing
- Will not share