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About
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.
Full description
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.
Enrollment
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Inclusion criteria
Histologically confirmed malignancy that is considered surgically incurable with either:
Confirmed IL13Ralpha2 tumor expression by immunohistochemistry (immunohistochemical assay [IHA] H-Score >= 50 in at least 10% of the total tumor specimen and in at least two high-power fields)
Age greater than or equal to 18 years old and less than 70 years old
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
A minimum of one measurable lesion defined as:
Absolute neutrophil count (ANC) >= 1 x 10^9 cells/L (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
Platelets >= 75 x 10^9/L (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
Hemoglobin >= 9.5 g/dL (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal (ULN) (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
Total bilirubin =< 2 x ULN (except patients with documented Gilbert's syndrome) (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
Creatinine < 2 mg/dL (or a glomerular filtration rate > 45) (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
Patients with melanoma must have progressed following >= 1 line of systemic therapy, including immune checkpoint inhibitor and a BRAF inhibitor in combination with MEK inhibitor for patients with BRAF V600-activating mutation and is not considered to have an alternate treatment option with curative intent
Must be willing and able to accept at least one leukapheresis procedure (This does not apply for patients receiving a second infusion of IL13R a2 CAR T cells as they will not undergo leukapheresis)
Must be willing and able to provide written informed consent
Exclusion criteria
Primary purpose
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18 participants in 1 patient group
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Central trial contact
Jacob Naparstek
Data sourced from clinicaltrials.gov
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