Trials / Recruiting

RecruitingNCT02133196

T Cell Receptor Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer

A Phase II Study Using Autologous Young Tumor-Infiltrating Lymphocytes Derived From Patients With Non-Small Cell Lung Cancer Following Non-Myeloablative Lymphocyte Depleting Preparative Regimen

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 85 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years – 72 Years
Healthy volunteers: Not accepted

Summary

Background: The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 100 patients. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause non-small cell lung cancer (NSCLC) tumors to shrink and to see if this treatment is safe. Eligibility: \- Adults age 18-72 with NSCLC who have a tumor that can be safely removed. Design: * Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed * Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product. * Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} * Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Detailed description

Background: * Patients with metastatic non-small cell lung cancer (NSCLC) have few approved therapeutic options and those that exist are of transient benefit. * Recent clinical experiences with experimental agents that release checkpoints on the host immune response (such as anti-PD-1 and anti-PDL1 antibody) have induced tumor regressions in patients with NSCLC. * Data from sequencing the genomes of human cancers have shown that, like malignant melanoma, NSCLC has a very high rate of tumor-specific genomic mutation. * In metastatic melanoma, a tumor infiltrating lymphocyte cell therapy product (TIL) can mediate the regression of bulky disease at any site when administered to an autologous patient with high dose aldesleukin following a non-myeloablative but lymphodepleting chemotherapy preparative regimen. * Recent studies on tumor infiltrating lymphocytes from melanoma have demonstrated that they can frequently recognize tumor-specific mutated proteins as "foreign" antigens and that is one hypothesis as to why melanoma is such an immunogenic tumor. * We propose to investigate the feasibility, safety, and efficacy of growing and administering an autologous tumor infiltrating lymphocyte product (TIL) to patients with metastatic NSCLC Objectives: Primary objective: -To determine the rate of tumor regression in patients with advanced non-small cell lung cancer (NSCLC) who receive an autologous tumor infiltrating lymphocyte product (TIL) plus aldesleukin following a lymphodepleting preparative regimen. Eligibility: * Patients who are \>= 18 years of age and \<= 72 years of age must have: * Advanced NSCLC refractory to standard therapy * A site of tumor that can be excised with minimal morbidity and mortality or that requires excision for clinical indications * At least one remaining site of measurable disease * Normal basic laboratory values. * Patients may not have: * Concurrent major medical illnesses that preclude aldesleukin administration or immunosuppression; * Severe hepatic function impairment due to liver metastatic burden; * Any form of immunodeficiency; * Severe hypersensitivity to any of the agents used in this study; * Symptomatic brain metastases or more than 3 CNS metastases Design: * Patients will undergo biopsy or resection to obtain tumor for generation of autologous tumor infiltrating lymphocyte cultures and autologous cancer cell lines. * The TIL product will be generated according to current TIL-lab standard operating procedures, using interleukin-2 and OKT3 antibody. * All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine * Cohort 1 will receive TIL on day 0 and then begin high-dose aldesleukin (720,000 IU/kg IV); cohort 2 will receive TIL on day 0 and then begin low-dose aldesleukin (72,000 IU/kg IV). Assignment to this cohort will be made if there are concomitant medical conditions that would preclude the use of high-dose aldesleukin * Clinical and immunologic response will be evaluated about 4-6 weeks after TIL infusion. * For both cohorts 1 and 2, using a Phase II design, 21 patients will be initially enrolled in each group to assess toxicity and tumor responses. If two or more of the first 21 patients per group show a clinical response (PR or CR), accrual will continue to 41 patients, targeting a 20% goal for objective response. In order to allow for a small number of non evaluable patients, a total of 85 patients may be enrolled over 5 years.

Conditions

Interventions

Type	Name	Description
DRUG	Aldesleukin	Aldesleukin 720,000 (Arm 1) or 72,000 (Arm 2) IU/kg IV (based on total body weight) over 15 minutes every 8 hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to a maximum of 9 doses in Arm 1 and 12 doses in Arm 2.
DRUG	Fludarabine	Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
DRUG	Cyclophosphamide	Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W with Mesna 15 mg/kg/day X 2 days over 1 hour.
BIOLOGICAL	Young TIL	Day 0: Cells will be infused intravenously (IV) on the Patient Care Unit over 20-30 minutes.

Timeline

Start date: 2014-10-23
Primary completion: 2027-10-23
Completion: 2027-10-23
First posted: 2014-05-07
Last updated: 2026-03-24

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT02133196. Inclusion in this directory is not an endorsement.