Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
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|ClinicalTrials.gov Identifier: NCT04715191|
Recruitment Status : Not yet recruiting
First Posted : January 20, 2021
Last Update Posted : January 20, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Liver Cancer Rhabdomyosarcoma Malignant Rhabdoid Tumor Liposarcoma Wilms Tumor Yolk Sac Tumor||Genetic: CARE T cells Drug: Cytoxan Drug: Fludara||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressing Autologous T Cells as an Immunotherapy for Children With Solid Tumors (CARE)|
|Estimated Study Start Date :||July 2022|
|Estimated Primary Completion Date :||August 2025|
|Estimated Study Completion Date :||July 2040|
Experimental: CARE T cells + Fludarabine and Cytoxan
GPC3-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.
Genetic: CARE T cells
Three different dosing schedules will be evaluated. The following dose levels will be evaluated:
DL1: 1x10^8/m2 DL2: 3x10^8/m2 DL3: 1x10^9/m2
The doses are calculated according to the actual number of GPC3-CAR transduced T cells.
Other Name: 15.21.GPC3-CAR T cells
Cyclophosphamide will be given at a dose of 500 mg/m2/day for 3 days given intravenously.
Other Name: Cyclophosphamide
Fludarabine will be given at a dose of 30 mg/m2/day for 3 days given intravenously.
Other Name: Fludarabine
- 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.
- 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
- Median T cell persistence [ Time Frame: 15 years ]T cell persistence will be measured by PCR
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): NCT04715191
|Contact: Andras Heczey||(832) firstname.lastname@example.org|
|Contact: David Steffin||(832) email@example.com|
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Andras Heczey, MD||Baylor College of Medicine|
|Principal Investigator:||David Steffin, MD||Baylor College of Medicine|