Gene Modified Immune Cells (IL13Ralpha2 CAR T Cells) After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma
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|ClinicalTrials.gov Identifier: NCT04119024|
Recruitment Status : Suspended (SAE review)
First Posted : October 8, 2019
Last Update Posted : July 23, 2020
|Condition or disease||Intervention/treatment||Phase|
|Clinical Stage IV Cutaneous Melanoma AJCC v8 IL13RA2 Positive Metastatic Melanoma Cutaneous Melanoma, Stage III Cutaneous Melanoma, Stage IV||Drug: Cyclophosphamide Drug: Fludarabine Phosphate Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells Drug: Recombinant Interleukin-2||Phase 1|
I. Clinical response. II. Chimeric antigen receptor (CAR) T-cell tumor infiltration and persistence. III. Impact of IL-2 on the persistence and tumor infiltration of IL13Ralpha2 CAR T cells.
I. Cytokine release syndrome analysis. II. Evaluation of endogenous anti-tumor immune response.
OUTLINE: This is a dose-escalation study of IL13Ralpha2-specific hinge-optimized 4-1BB-co-stimulatory CAR/truncated (Cluster of Differentiation 19) CD19-expressing autologous TN/MEM cells (IL13Ralpha2 CAR T cells).
Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -5 to -4 and fludarabine phosphate IV over 15-30 minutes on days -4 to -1. Patients then receive IL13Ralpha2 CAR T cells IV on day 0. Patients may also receive recombinant interleukin-2 subcutaneously (SC) twice daily (BID) on days 1-7.
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 (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1 Dose Escalation Study of Systemically Administered IL13Ra2 Chimeric Antigen Receptor (CAR) T Cells After a Nonmyeloablative Conditioning Regimen in Patients With Metastatic Melanoma|
|Actual Study Start Date :||November 27, 2019|
|Estimated Primary Completion Date :||October 1, 2024|
|Estimated Study Completion Date :||October 1, 2025|
Experimental: Treatment (chemotherapy, IL13Ralpha2, Il-2)
Patients receive cyclophosphamide IV over 1 hour on days -5 to -4 and fludarabine phosphate IV over 15-30 minutes on days -4 to -1. Patients then receive IL13Ralpha2 CAR T cell IV on day 0. Patients may also receive recombinant interleukin-2 SC BID on days 1-7.
Drug: Fludarabine Phosphate
Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells
Drug: Recombinant Interleukin-2
- Incidence of adverse events [ Time Frame: Up to 90 days from the day of CAR-transgenic cell infusion ]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.
- Dose-limiting toxicity (DLT) [ Time Frame: Up to 90 days from the day of CAR-transgenic cell infusion ]
- Objective response rate [ Time Frame: Up to 120 days ]Will be recorded following the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- Complete response [ Time Frame: At day 60, 120, and every 2-3 months for up to 2 years ]
- Partial response [ Time Frame: At day 60, 120, and every 2-3 months for up to 2 years ]
- Response for in-transit metastasis [ Time Frame: Up to 2 years ]
- Time to disease progression [ Time Frame: 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 ]
- 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 ]
- Impact of IL-2 on systemic persistence of CAR T cells [ Time Frame: Up 2 years ]
- Impact of IL-2 on tumor infiltration of CAR T cells [ Time Frame: Up 2 years ]
- Cytokine release syndrome analysis [ Time Frame: Up 2 years ]Plasma or serum collected from the blood at multiple time points after CAR T cell infusion will be frozen and banked; cytokine levels will be quantified in patients exhibiting any > grade-2 CRS.
- Evaluation of an endogenous T cell anti-tumor response [ Time Frame: Up 2 years ]The biopsies will be analyzed by hematoxylin and eosin staining (H&E), immunohistochemistry (IHC) to quantify the numbers of T lymphocytes. If sufficient quantity of tissue is available, the study investigators will attempt to monitor the phenotype of the TIL obtained from tumor biopsy samples by multicolor flow cytometry (FACS), and other immune monitoring assays.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04119024
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|UCLA / Jonsson Comprehensive Cancer Center|
|Los Angeles, California, United States, 90095|
|Principal Investigator:||Anusha Kalbasi||UCLA / Jonsson Comprehensive Cancer Center|