Gene Modified Immune Cells After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma or Metastatic Solid Tumors

Brief summary public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Procedure: Biopsy. Undergo biopsy

Intervention public domain (ClinicalTrials.gov)

Procedure: Biospecimen Collection. Undergo collection of blood samples

Intervention public domain (ClinicalTrials.gov)

Procedure: Computed Tomography. Undergo CT scan

Intervention public domain (ClinicalTrials.gov)

Drug: Cyclophosphamide. Given IV

Intervention public domain (ClinicalTrials.gov)

Drug: Fludarabine Phosphate. Given IV

Intervention public domain (ClinicalTrials.gov)

Other: Fludeoxyglucose F-18. Undergo FDG-PET/CT scan

Intervention public domain (ClinicalTrials.gov)

Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells. Given IV

Intervention public domain (ClinicalTrials.gov)

Procedure: Magnetic Resonance Imaging. Undergo MRI

Arm public domain (ClinicalTrials.gov)

Treatment (chemotherapy, IL13Ralpha2) (experimental): Patients may receive cyclophosphamide 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, CT, or 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.

Primary outcome public domain (ClinicalTrials.gov)

Incidence 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.

Primary outcome public domain (ClinicalTrials.gov)

Dose-limiting toxicity. Time frame: Up to 28 days from the day of CAR-transgenic cell infusion.

Secondary outcome public domain (ClinicalTrials.gov)

Objective response rate. Time frame: Up to 120 days.

Secondary outcome public domain (ClinicalTrials.gov)

Complete response (CR). Time frame: At day 30, 60, 120, and every 2-3 months for up to 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Partial response (PR). Time frame: At day 60, 120, and every 2-3 months for up to 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

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.

Secondary outcome public domain (ClinicalTrials.gov)

Response for in-transit metastasis. Time frame: Up to 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

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.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Histologically confirmed malignancy that is considered surgically incurable with either: * Stage IIIC melanoma including locally relapsed, satellite, in-transit lesions or bulky draining node metastasis * Stage IV melanoma including patients with known brain metastases * Other metastatic, non-central nervous system (CNS) solid tumor relapsed or refractory after all standard-of-care systemic therapies for which the patient is eligible * 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 75 years old * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * A minimum of one measurable lesion defined as: * Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), OR * Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s) * 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 …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 18 participants (estimated).