Tumor-Infiltrating Lymphocytes And Low-Dose Interleukin-2 Therapy Following Cyclophosphamide And Fludarabine In Patients With Melanoma

Study Overview
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Brief Summary
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This is a phase II clinical study for patients with metastatic (the cancer has spread to other parts of the body) melanoma. Patients will receive an infusion (given by vein) of autologous tumor infiltrating lymphocytes (TILs). TILs are a type of white blood cells that recognizes tumor cells and enter them which causes the tumor cells to break down. Prior to the cell infusion, patients will receive a two drugs cyclophosphamide and fludarabine to prepare the body to receive the TILs. After cell infusion, patients will receive low-dose interleukin-2 therapy which is an approved drug to treat melanoma. This study will see how useful this regimen is in treating metastatic melanoma.

Official Title
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Phase II Study Evaluating The Infusion Of Autologous Tumor-Infiltrating Lymphocytes (TILs) And Low-Dose Interleukin-2 (IL-2) Therapy Following A Preparative Regimen Of Non-Myeloablative Lymphodepletion Using Cyclophosphamide And Fludarabine In Patients With Metastatic Melanoma

Conditions
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Metastatic, Stage III or Stage IV, Melanoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Fludarabine
* Biological: Tumor-Infiltrating Lymphocytes
* Biological: Low-Dose Interleukin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Eligibility for TIL Evaluation): Must have measurable, unresectable stage III or stage IV melanoma Suitable tumor for collection If tumor is suitable for collection, patient must be suitable for surgery Patient must be 18 years of age or older Performance status of ECOG 0 or 1 Life expectancy > 5 months from date of consent of TIL evaluation Willing to be tested for transmissible diseases For patients with a history of allergy to penicillin, gentamycin, streptomycin, or anti-fungals, the ability to generate TILs will be confirmed with the cell manufacturing laboratory Inclusion Criteria (Eligibility for Treatment): Signed and dated the informed consent No brain metastases or stable brain metastases for 3 months following definitive treatment. Life expectancy > 3 months from the date of consent for TILs treatment TILs are suitable for use as determined by laboratory More than 30 days since any prior systemic therapy at the time of the cell infusion, or more than six weeks since prior nitrosurea therapy. For patients with prior ipilimumab therapy, at least six weeks must elapse between the last ipilimumab dose and the start of study treatment. All side effects from previous treatment must have recovered to an acceptable grade level. Adequate organ function Must have positive EBV titres Women of child-bearing potential must have a negative pregnancy test. Patients of both genders must be willing to practice birth control during treatment and for 6 months post completion of IL-2 treatment. Exclusion Criteria: Requiring systemic steroid therapy HIV positive With active hepatitis B or hepatitis C, syphilis, or HTLV Must not have any active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, uncontrolled psychiatric disorders, or other conditions that may affect following study procedures. Have no active underlying cardiac illnesses defined by positive stress test, LVEF<40% or ongoing life-threatening arrhythmias Abnormal lung function test

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclophosphamide and Fludarabine followed by TILs and IL-2<br>Cyclophosphamide, i.v., 60mg/kg per day for 2 days and Fludarabine, i.v., 25mg/m2 per day for 5 days; then Tumor-Infiltrating Lymphocytes, i.v., 1x10^10 - 1.6x10^11 cells and Low-Dose Interleukin, i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week) | Drug: Cyclophosphamide<br>* i.v., 60mg/kg per day for 2 days<br>* Other names: CYTOXAN, PROCYTOX;Drug: Fludarabine<br>* i.v., 25mg/m2 per day for 5 days<br>* Other names: FLUDARA;Biological: Tumor-Infiltrating Lymphocytes<br>* i.v., 1x10^10 - 1.6x10^11 cells<br>Biological: Low-Dose Interleukin<br>* i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week)<br>* Other names: Aldesleukin, Proleukin, Recombinant Human Interleukin 2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response to treatment |  | 6 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number occurrences and severity of side effects |  | Starting at first dose of study treatment up to 10 years | 
| Number of patients with an immunity and no immunity to the study treatment |  | From start of study up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage IV, Measurable, Unresectable, Stage III, Metastatic, Melanoma, Tumor-Infiltrating Lymphocytes, Low-Dose Interleukin-2, Cyclophosphamide, Fludarabine