Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Ipilimumab

Interleukin-2

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.

Pre-treatment with ipilimumab (cycle 1): Before the participant's tumor sample is taken to send to the lab for growing the TILs, they will start their first cycle of ipilimumab. This drug is given as an intravenous infusion (through a vein) over a period of about 90 minutes (an hour and a half). Cycle 2 of ipilimumab: About a week after the sample of the participant's tumor was collected for TIL growth (and 3 weeks after their first cycle of ipilimumab), participants will have their second cycle of ipilimumab. This will be another IV infusion, lasting about 90 minutes.

Tumor sample for TIL growth in the lab: About 2 weeks after the participant's first cycle of ipilimumab, a sample of their tumor will be collected and sent to the lab for TIL growth. Growing the TILs takes about 6 weeks. If their sample has grown enough TIL cells, participants will continue with the next part of the study. Depending on how long the TILs take to grow in the lab, they may need to repeat some of their laboratory and imaging tests (blood draws, X-rays, and CT or magnetic resonance imaging \[MRI\] scans). TIL Infusion (inpatient): After completing lymphodepletion, participants will be admitted back into the hospital for IV infusion of the TIL cells.

Tumor Infiltrating Lymphocytes (TIL)

Lymphodepletion (inpatient hospital stay for about 2 days plus outpatient drug dosing for 5 days): About 4 weeks after their second cycle of ipilimumab, participants will be admitted to the hospital for their first two days of receiving the chemotherapy drug, cyclophosphamide. This drug will be given as an intravenous (IV, meaning through the vein) infusion. After 2 days of receiving cyclophosphamide, if their study doctor thinks that they are well enough, you will be discharged from the hospital and will return for the next 5 days in a row for outpatient IV infusions of the second lymphodepletion chemotherapy, fludarabine.

Administration of Lymphodepletion

Cyclophosphamide as Part of Lymphodepletion

Fludarabine as Part of Lymphodepletion

High dose IL-2 (continued inpatient): Participants will remain in the hospital following TIL infusion for receiving high dose IL-2 and recovery. The IL-2 will be given three times per day for about 3-5 days as an IV bolus (meaning through the vein, more quickly than other infusions - in about 15 minutes each dose). Participants will remain in the hospital for approximately 7-14 days until they have recovered from the IL-2 treatments.

High Dose IL-2

Adoptive Cell Therapy with TIL

Amod Sarnaik, M.D.

Purpose of this Pilot Study: The investigators want to study the safety, side effects, and benefits of tumor infiltrating lymphocytes (TILs), when they are given with the drug ipilimumab. Ipilimumab 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.

The primary endpoints of this pilot trial will be the safety and feasibility of administering ipilimumab with Adoptive Cell Therapy (ACT) using TIL. The data analysis will mainly be descriptive. All study results will be preliminary and of exploratory in nature due to the pilot status and small sample size of the trial. Feasibility is defined as the ability to deliver at least 50% (i.e., two out of four) of the planned doses of ipilimumab and successfully treat at least 60% (i.e., ≥ 6/10) of the patients with TIL. All participants will be evaluable for toxicity from the time of their first protocol treatment. Toxicity will be reported by type and severity according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.

Ipilimumab With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Melanoma Mets Pts

Co-stimulation With Ipilimumab to Enhance Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Patients With Metastatic Melanoma

Occurrence of adverse events with dose limiting toxicity, per adverse event category.

Number of participants who were successfully treated with at least 2 doses of ipilimumab and received TIL. Feasibility is defined as the ability to deliver at least 50% (i.e., two out of four) of the planned doses of ipilimumab and successfully treat at least 60% (i.e., ≥ 6/10) of the patients with TIL.

Overall Response: Complete Response (CR) + Partial Response (PR), per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 for target lesions and assessed by computed tomography (CT) scan. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions..

Progression-free survival (PFS) per RECIST V1.1, defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Progressive Disease (PD): At least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum recorded since the treatment started or the appearance of one or more new lesions.

Bristol-Myers Squibb

Iovance Biotherapeutics, Inc.

H. Lee Moffitt Cancer Center and Research Institute

Experimental: Combination Therapy

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

All participants (13). All evaluable participants (12) may be referenced for some outcome measures.

Spots Global Cancer Trial Database for cyclophosphamide as part of lymphodepletion