Investigators plan to study the safety, side effects, and benefits of tumor-infiltrating lymphocytes (TILs) when they are given with the drug nivolumab. Nivolumab is a type of immunotherapy - a drug that is used to boost the ability of the immune system to fight cancer, infection, and other diseases.
In this study, these special immune T-cells will be taken from a sample of the participant's tumor tissue that will be surgically removed. Certain parts of these cells will be multiplied, or grown, in the laboratory, using the drug interleukin-2 (IL-2) during part of the process. They will then be given back to the participant by an infusion in their veins. These cells are called tumor- infiltrating lymphocytes (TILs). The use of TILs involves a combination of drugs, including the following: * Fludarabine and cyclophosphamide - two types of chemotherapy drugs. These drugs will be used for what is called lymphodepletion. The purpose of lymphodepletion in this study is to temporarily reduce the number of normal lymphocytes circulating in the participant's body before they are given the TILs that were grown in the lab. This is so that there will be more "space" for the lymphocytes (TILs) that will be infused in their veins. * Interleukin-2 (IL-2) - a drug used to help the body's response to treatment on the immune system. A high dose regimen of IL-2 will be given after the participant receives the infusion of the T-cells.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Tumor harvest for TIL growth in the lab: A sample of the participant's tumor will be collected and sent to the lab for TIL growth. TIL will be prepared and cryopreserved.
Nivolumab will be administered intravenously at a fixed dose of 240 mg for 4 doses every 2 weeks prior to TIL. Nivolumab dose will be fixed at 480 mg every 4 weeks up to 12 months after TIL.
Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS) over approximately 2 hours. Cyclophosphamide will be initiated seven days prior to the anticipated TIL transfer, and the precise timing will depend on the rate of in vitro TIL growth. The dose will be based on the patient's body weight, but to prevent undue toxicity, it will not exceed a dose greater than 140% of the maximum ideal body weight per Metropolitan Life Insurance Company, Height and Weight Table.
After administration of Cyclophosphamide, Fludarabine will then be infused at 25 mg/m\^2 intravenous piggyback (IVPB) daily over approximately 30 minutes starting 5 days prior to TIL transfer. To prevent undue toxicity with fludarabine, the dose will be based on body surface area (BSA), but will not exceed a dose calculated on surface areas based on body weights greater than 140% of the maximum ideal body weight per Metropolitan Life Insurance Company Height and Weight Tables.
On day 0, all patients will receive TIL administered according to the current Moffitt Cell Therapy TIL Standard Operating Procedure (SOP). Eight (8) to twelve (12) hours after completing the TIL infusion, all participants will begin intermediate-dose decrescendo interleukin-2 (IL-2).
Interleukin-2 (IL-2) - a drug used to help the body's response to treatment on the immune system. A high dose regimen of IL-2 will be given after the infusion of the T-cells.
University of Florida Health Cancer Center.
Gainesville, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Rate of Dose Limiting Toxicity (DLT)
Investigators plan to demonstrate that treatment with nivolumab in patients undergoing TIL therapy is safe with a continuous Pocock-type stopping boundary for serious toxicity of \< 17%, with safety reported based upon Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. DLT defined as: any grade ≥3 immune-related adverse event definitely attributable to nivolumab. DLT related to adoptive cell therapy will be defined as a non-hematologic grade 4 or higher adverse event that is immediately life-threatening occurring upon or after the start of therapy that is immediately life-threatening and not related to non-small cell lung cancer or other pre-existing condition. Safety: Toxicity will be assessed within 4 weeks of the adoptive TIL transfer. The accrual will be halted if excessive numbers of participants with toxicity are seen. For example, if there are 5 or more out of 10 participants (full follow-up) with toxicity, the trial will be stopped.
Time frame: Up to 40 months
Number of Participants With Objective Response
Participants displaying objective response associated with the treatment regimen per Response Evaluation Criteria in Solid Tumors (RECIST v.1.1). The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
Time frame: Up to 40 months
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