GPC-3 CAR T CELLS FOR Recurrent GPC-3 Positive Glioblastoma
ConditionGlioblastoma Multiforme of Brain
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age21-70
SponsorBaylor College of Medicine
About this trial
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 participants with cancers. They have shown promise, but have not been strong enough to cure most participants.
The study team has found from previous research that we can put a new gene (a tiny part of what makes-up DNA and carries the participants traits) into T cells that will make them recognize cancer cells and kill them. In the lab, the study team has made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33. The antibody GC33 recognizes a protein found on the participants brain tumor. This CAR is called GPC3-CAR. To make this CAR more effective, the study has also added a gene that includes IL15. IL15 is a 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 killed tumor cells better in the laboratory when compared with CAR T cells that did not have IL15. This study will test T cells with the IL15 GPC3-CAR (GO-CART T cells) in participants with GPC3-positive brain tumors.
T cells made to carry a gene called iCasp9 can be killed when they encounter a specific drug called AP1903. The study team 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 study team 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 (GO-CART T cells) in participants with GPC3-positive brain tumors.
The GO-CART T cells are an investigational product not approved by the Food and Drug Administration.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of GPC3-positive recurrent glioblastoma with previous resection planned for repeat resection (as determined by immunohistochemistry).
Age ≥18 years
Karnofsky score ≥60%
Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
Disqualifiers
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).
Trial design
Design model
Single group
Treatments tested in this trial
15.GPC3-CAR T cells
GeneticFour different dosing schedules will be evaluated. The following dose levels will be evaluated: DL1: 5x10\^6 DL2: 1x10\^7 DL3: 5x10\^7 DL4: 1x10\^8
Treatment groups
27 Participants
are divided into 1 treatment groupGroup A: 15.GPC3-CAR T cellsExperimental treatment 1 intervention
Trial outcomes
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 15.GPC3-CAR T cells. Specifically those which are Grade 5; hematologic dose-limiting toxicity is any Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours; Grade 4 allergic reaction to CAR T cell administration; Grade 4 \\reactions due to CRS and neurotoxicity are rarely 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 72 hours. Grade 4 CRS and neurologic toxicities will be reported to the FDA in an expedited fashion.
Time frame
4 weeksSecondary outcomes
1
Response Rate
Response rates will be estimated as the percent of patients whose best response is either complete response or partial by combining the data from lesions recorded via imaging for each patient pre- and post-15.GPC3-CAR T-cell intracavitary administration. These data will be evaluated by iRANO criteria. A 95% confidence interval will be calculated for the response rate.
Time frame
4 weeks2
Maximum Tolerated Dose (MTD)
The maximum tolerated dose (MTD) is determined based on isotonic regression as specified in Liu and Yuan (PMID: 3162195). The dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there is no DLT that determine a MTD, the maximum dose level will be declared as the MTD. In case the lowest dose level is determined to be too toxic and the elimination boundary is reached, no MTD will be defined for the trial.
Time frame
4 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Baylor College of Medicine
Lead sponsor
Center for Cell and Gene Therapy, Baylor College of Medicine
Collaborator
Baylor St. Luke's Medical Center
Collaborator
Source ClinicalTrials.gov