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Tumor-Infiltrating Lymphocytes After Combination Chemotherapy in Treating Patients With Metastatic Melanoma

Complete title: Cellular Adoptive Immunotherapy Using Autologous Tumor-Infiltrating Lymphocytes Following Lymphodepletion with Cyclophosphamide and Fludarabine For Patients With Metastatic Melanoma

Research Study Number       2643.00
    
Principal Investigator       Sylvia Lee, MD
    
Phase       II

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Research Study Description

This phase II trial studies how well tumor-infiltrating lymphocytes after combination chemotherapy works in treating patients with metastatic melanoma. Biological therapies, such as tumor-infiltrating lymphocytes, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving tumor-infiltrating lymphocytes after combination chemotherapy may kill more tumor cells

Eligibility Criteria (must meet the following to participate in this study)

Ages Eligible for Study: 18 Years and older

Genders Eligible for Study: Both

- Step I Inclusion Criteria:

- * Stage IV melanoma or stage III melanoma that is unlikely to be cured by surgery

- * Able to tolerate high-dose cyclophosphamide, fludarabine and high-dose IL-2

- * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- * Patients must have an magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET) of the brain within 2 months before consenting; if new lesions are present, principal investigator (PI) or designee should make final determination regarding enrollment

- * Patients must have a site of metastatic disease that can be safely resected or biopsied for tissue sufficient for TIL harvest

- * A stress cardiac test (e.g., stress treadmill, stress thallium, stress multi gated acquisition scan [MUGA], dobutamine echocardiogram) to rule out cardiac ischemia within 4 months before Step I is required for all patients with underlying risk factors such as diabetes or hypertension, or who have a history of cardiac disease

- Step II Inclusion Criteria:

- * Patients must have measurable metastatic melanoma

- * Able to tolerate high-dose cyclophosphamide, fludarabine, and high-dose IL-2

- * ECOG performance status of 0-1 at time of lymphodepletion

- * Patients must have brain imaging by MRI, CT or PET within 30 days prior to lymphodepletion; patients may have up to 2 asymptomatic brain lesions < 1cm each; 1-3 lesions that are > 1cm that have been irradiated and in the opinion of the investigator no longer represents active disease will also be allowed

- * A stress cardiac test (e.g., stress treadmill, stress thallium, stress MUGA, dobutamine echocardiogram) to rule out cardiac ischemia within 4 months prior to lymphodepletion is required for all patients

- * Pulmonary function tests (PFTs) are required of all patients within 4 months prior to lymphodepletion; forced expiratory volume (FEV)1 and forced vital capacity (FVC) must be >= 65% predicted and diffusion lung capacity for carbon monoxide (DLCO) must be >= 50% predicted

- * Patients must have their tumor sent for BRAF mutational analysis; patients must have adequate TIL (at least 40 x 106 cells at the pre-expansion stage)

Other eligibility criteria may apply.

Exclusions (conditions that would prevent participation in this study)

- Step I Exclusion Criteria:

- * Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence for 4 months after treatment

- * Calculated creatinine clearance (estimated glomerular filtration rate [eGFR]) < 60ml/min

- * Significant hepatic dysfunction (aspartate aminotransferase [AST]/alanine aminotransferase [ALT] > 3 x upper limit of normal

- * Total bilirubin > 2.0 mg/dl, except in patients with Gilbert's Syndrome whose total bilirubin must not exceed 3.0 mg/dl) deemed by investigator to be irreversible

- * Forced expiratory volume in 1 second [FEV1] < 65% predicted, forced vital capacity (FVC) < 65% of predicted, diffusing capacity of lung for carbon monoxide (DLCO) (corrected for hemoglobin [Hgb]) < 50% predicted); pulmonary function tests (PFTs) within 4 months prior to consent for Step I will be required for patients with underlying risk factors such as smoking history, or history of lung disease

- * Significant cardiovascular abnormalities as defined by any one of the following:

- ** Congestive heart failure,

- ** Clinically significant hypotension, cardiac ischemia, or symptoms of coronary artery disease,

- ** Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy,

- ** Ejection fraction < 45% (echocardiogram or MUGA), although any patient with an ejection fraction between 45-49% must receive clearance by a cardiologist to be eligible for this trial

- * Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to be HIV antibody seropositive or known to be recently polymerase chain reaction (PCR)+ for hepatitis B or C are not eligible for this study; the severely depressed or altered immune system found in these patients and the possibility of premature death would compromise study objectives

- * Patients with active systemic infection requiring intravenous antibiotics

- * Clinically significant psychiatric disease which, in the opinion of the PI or sub-I, would render immunotherapy and its potential sequelae unsafe or compliance with procedural requirements unlikely

- Step II Exclusion Criteria:

- * Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within 7 days prior to entry; patients of both genders must practice birth control during treatment and for four months after treatment

- * Calculated creatinine clearance (eGFR) < 60ml/min

- * AST/ALT > 3 x upper limit of normal

- * Total bilirubin > 2.0 mg/dl, except in patients with Gilbert's Syndrome whose total bilirubin must not exceed 3.0 mg/dl)

- * Clinically significant pulmonary dysfunction (FEV1< 65% predicted or FVC < 65% of predicted, DLCO (corrected for Hgb) < 50% predicted)

- * Significant cardiovascular abnormalities as defined by any one of the following:

- ** Congestive heart failure,

- ** Clinically significant hypotension,

- ** Cardiac ischemia, or symptoms of coronary artery disease,

- ** Presence of cardiac arrhythmias on EKG requiring drug therapy,

- ** Ejection fraction < 45% (echocardiogram or MUGA), although any patient with an ejection fraction between 45-49% must receive clearance by a cardiologist to be eligible for this trial

- * Absolute neutrophil count less than 1000/mm^3

- * Platelet count less than 100,000/mm^3

- * Hemoglobin less than 10.0g/dl

- * Untreated central nervous system metastases that are either symptomatic or greater than 1 cm at time of therapy; 1-3 lesions that are > 1cm that have been treated with stereotactic radiosurgery (SRS) and in the opinion of the PI or sub-I no longer represent active disease may be allowed

- * Patients with systemic infections requiring active therapy within 72 hours of lymphodepletion

- * Systemic cancer therapy (standard or experimental), including cytotoxic chemotherapy or IL-2, received less than 4 weeks or checkpoint blocking agents (e.g., CTLA-4 or PD1/PD-L1 inhibitors) received less than 6 weeks prior to lymphodepletion, with the exception of targeted therapies

- * Commercially available, molecularly targeted therapies (e.g., vemurafenib, imatinib) taken within 7 days prior to lymphodepletion

- * Clinically significant autoimmune disorders or conditions of immunosuppression; patients with AIDS or HIV-1 associated complex or known to HIV antibody seropositive or known to be recently PCR+ for hepatitis B or C virus are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed or altered immune system found in these patients and the possibility of premature death would compromise study objectives

- * Prior treatment with systemic steroids within 4 weeks prior to lymphodepletion (except for physiologic replacement doses for adrenal insufficiency) or topical steroids within 2 weeks prior to lymphodepletion

- * Any other significant medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the PI

Other exclusion criteria may apply.



Research Study Number       2643.00
    
Contact       Seattle Cancer Care Alliance Intake Office
    
Telephone       800-804-8824 / 206-288-1024
    
   

Keywords
Melanoma; Solid Tumors

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