A Study Using Tumor-Reactive Autologous Tumor Infiltrating Lymphocytes (TIL) in Metastatic Melanomas

NCT ID: NCT02375984

Last Updated: 2021-09-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-16
• Study Completion Date: 2017-06-01

Brief Summary

The purpose of this protocol is to determine whether autologous TIL infused in conjunction with systemic high-dose IL-2 after non-myeloablative chemotherapy with cyclophosphamide and fludarabine can cause consistent and durable objective responses in patients who have metastatic melanoma at the John Wayne Cancer Institute (JWCI).

Conditions

Metastatic Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tumor Infiltrating Lymphocytes (TIL)

Patients will have a melanoma metastasis resected and cultured in IL-2 in vitro either as part of this treatment protocol or the JWCI procurement protocol. TIL from these cultures will be assessed for tumor-reactivity and those with such activity will be further expanded and adoptively transferred. Patients will receive a non-myeloablative lymphocyte-depleting preparative regimen consisting of cyclophosphamide (60 mg/kg/day X 2 days IV) and fludarabine (25 mg/m2/day IV X 5 days). Following this regimen, patients will receive an intravenous adoptive transfer of at least 109 tumor-reactive lymphocytes (TIL) followed by high-dose intravenous IL-2 (600-720,000 IU/kg/dose every 8 hours for up to 12 doses).

Group Type: EXPERIMENTAL

Tumor Infiltrating Lymphocytes (TIL)

Intervention Type: BIOLOGICAL

Patients will receive an IV adoptive transfer of at least 10\^9 tumor-reactive lymphocytes. An IV catheter in the patient's arm or upper chest will be used for cell infusion. The TIL will be administered over 20-30 minutes at room temperature using a standard infusion protocol or by hanging the infusion bag from a stand and allowing gravity to pull the cells down.

Interventions

Tumor Infiltrating Lymphocytes (TIL)

Patients will receive an IV adoptive transfer of at least 10\^9 tumor-reactive lymphocytes. An IV catheter in the patient's arm or upper chest will be used for cell infusion. The TIL will be administered over 20-30 minutes at room temperature using a standard infusion protocol or by hanging the infusion bag from a stand and allowing gravity to pull the cells down.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patients must have metastatic melanoma with a resectable metastatic lesion of sufficient size and be willing to undergo such a resection for experimental purposes.
• Patients must be > 18 years of age.
• Patients must have measurable disease measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (in addition to the resected lesion).
• Patients of child bearing potential must agree to use an effective form of birth control during study and up to four months after receiving treatment.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-1.
• Absolute neutrophil count greater than 1000/mm3 without support of filgrastim.
• Platelet count greater than 100,000/mm3.
• Serum Alanine transaminase/Aspartate transaminase (ALT/AST) less than three times the upper limit of normal.
• Serum creatinine less than or equal to 1.6 mg/dl.
• Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dl.
• Patients must be able to understand and sign the Informed Consent document.

Exclusion Criteria

• All systemic, cytotoxic therapy (including targeted therapies) must be stopped at least 5 weeks prior to cell infusion (see 2.1.3).
• Women who are pregnant or breastfeeding.
• Life expectancy of less than three months.
• Patients who have received prior treatment with anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody will be excluded unless a post anti-CTLA-4 antibody treatment colonoscopy was normal with normal colonic biopsies.
• Patients who require immediate active treatment for symptomatic Central Nervous System (CNS) lesions will not be eligible until after treatment of their symptomatic lesions.

• Less than 5 weeks has elapsed since any prior systemic therapy at the time the patient receives the preparative regimen. All patients' toxicities must have recovered to a grade 1 or less or as specified in the eligibility criteria in Section 2.1.1. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 5 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria in Section 2.1.1.
• Women of child-bearing potential who are pregnant or breastfeeding.
• Life expectancy of less than three months.
• Systemic steroid therapy more than the equivalent of 10mg/day of prednisone.
• Hemoglobin less than 8g/dl unable to be corrected with transfusion.
• Any active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
• Any form of primary or secondary immunodeficiency. Must have recovered immune competence after chemotherapy or radiation therapy as evidenced by normal Absolute Neutrophil Count (ANC) > 1000/mm3 and absence of opportunistic infections. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
• Seropositive for HIV antibody.
• Patients with active hepatitis B or active hepatitis C.
• The following patients will be excluded because of inability to receive high dose proleukin:
• Patients will be excluded if they have a history of major EKG abnormalities, symptoms of cardiac ischemia or arrhythmias and have a Left Ventricular Ejection Fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress Multi Gated Acquisition Scan (MUGA), dobutamine, echocardiogram or other stress test)
• Patients who have a prolonged history of cigarette smoking or symptoms of respiratory dysfunction will be excluded if they have an abnormal pulmonary function test as evidenced by a Forced Expiratory Volume at one second Forced Expiratory Volume at one second (FEV1)< 60% predicted.
• Patients who have received prior treatment with anti-CTLA-4 antibody will be excluded unless a subsequent colonoscopy was normal with normal colonic biopsies (to rule out colitis).
• Patients who require immediate treatment for symptomatic CNS lesions will not be eligible until after treatment of their symptomatic lesions and resolution of symptoms.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Saint John's Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Faries, MD., FACS

Role: PRINCIPAL_INVESTIGATOR

Saint John's Cancer Institute

Locations

John Wayne Cancer Institute

Santa Monica, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

TIL-TREATMENT-0614

Identifier Type: -

Identifier Source: org_study_id