This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma or solid tumors that have spread to other places in the body (metastatic). The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patient's own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.
PRIMARY OBJECTIVE: I. To evaluate the safety of systemic administration of IL13Ralpha2-redirected CAR T cells, including determination of the maximum tolerated dose (MTD). SECONDARY OBJECTIVES: I. Clinical response. II. Determine the infiltration of IL13Ralpha2 CAR T cells into the tumor. III. Determine the persistence of IL13Ralpha2 CAR T cells in the peripheral blood. EXPLORATORY OBJECTIVES: I. Evaluate the induction of endogenous anti-tumor T cell responses in patients receiving IL13Ralpha2 CAR T cell therapy. II. Assess for the occurrence of cytokine release syndrome in patients receiving IL13Ralpha2 CAR T cells by evaluating plasma cytokine levels. OUTLINE: This is a dose-escalation study of IL13Ralpha2-specific hinge-optimized 4-1BB-co-stimulatory CAR/truncated CD19-expressing autologous TN/MEM cells (IL13Ralpha2 CAR T cells) followed by a dose-expansion study. Patients may receive cyclophosphamide intravenously (IV) over 60 minutes on days -5 to -3 and fludarabine phosphate IV over 15-30 minutes on days -5 to -2. Patients then receive IL13Ralpha2 CAR T cells IV on day 0. Patients also undergo biopsy at baseline and on study, computed tomography (CT), or positron emission tomography (PET) and CT scan at screening and on study, magnetic resonance imaging (MRI) throughout the trial, and collection of blood samples throughout the trial. Patients with disease progression may receive a second cycle with an infusion of IL13Ralpha2 CAR T cells. After completion of study treatment, patients are followed every 2-3 months for 2 years, every 6 months for 3 years, then every year for at least 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Undergo biopsy
Undergo collection of blood samples
Undergo CT scan
Given IV
Given IV
Undergo FDG-PET/CT scan
Given IV
Undergo MRI
Undergo PET scan
City of Hope
Duarte, California, United States
RECRUITINGUCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGStanford Cancer Institute
Stanford, California, United States
RECRUITINGIncidence of adverse events
Safety will be reported as incidence rates for adverse events, serious adverse events, and fatal adverse events for Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 3 or higher. Adverse events will be tabulated by treatment group and will include the number of patients for whom the event occurred, the rate of occurrence, and the severity and relationship to study drug.
Time frame: Up to 90 days from the day of chimeric antigen receptor (CAR)-transgenic cell infusion
Dose-limiting toxicity
Time frame: Up to 28 days from the day of CAR-transgenic cell infusion
Objective response rate
Will be recorded following the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Time frame: Up to 120 days
Complete response (CR)
Time frame: At day 30, 60, 120, and every 2-3 months for up to 2 years
Partial response (PR)
Time frame: At day 60, 120, and every 2-3 months for up to 2 years
Progression-free survival
Time frame: Time from study enrollment to the date of progressive disease first documented disease progression per RECIST v1.1 or death due to any cause by investigator assessment, whichever occurs first, assessed up to 2 years
Response for in-transit metastasis
Time frame: Up to 2 years
Time to disease progression
Time frame: The length of time from the date of CAR T cell infusion to the date of progressive disease first documented, death, or the start of secondary antitumor therapy, assessed up to 2 years
Overall survival
Time frame: From the date of CAR T cell infusion in the clinical trial until death, whether related to the trial or not, assessed up to 2 years
Duration of overall complete response
Time frame: From the time measurement criteria is met for CR until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
Duration of overall response
Time frame: From the time measurement criteria is met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
IL13Ralpha2 CAR T cell persistence
Time frame: At days 1, 7, 14, 30, 60, 90, and 120
IL13Ralpha2 CAR T Cell phenotypic monitoring
Time frame: Up 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.