Clinical Trials /

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

NCT02133196

Description:

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 18-70 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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: T Cell Receptor Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer
  • Official Title: A Phase II Study Using Autologous Young Tumor-Infiltrating Lymphocytes (TIL) Derived From Patients With Non-Small Cell Lung Cancer Following Non-Myeloablative Lymphocyte Depleting Preparative Regimen

Clinical Trial IDs

  • ORG STUDY ID: 140104
  • SECONDARY ID: 14-C-0104
  • NCT ID: NCT02133196

Conditions

  • Metastatic Non-Small Cell Lung Cancer
  • Squamous Cell Carcinoma
  • Advanced NSCLC
  • Adenosquamous Carcinoma
  • Adenocarcinomas

Interventions

DrugSynonymsArms
AldesleukinCohort 2
FludarabineCohort 1
CyclophosphamideCohort 1
Young TILCohort 1

Purpose

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 18-70 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 or older 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 shows 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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalPatients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by young TIL and high DoseAldesleukin (720,000 IU/Kg) IV every 8 hours for up to 9 doses.
  • Aldesleukin
  • Fludarabine
  • Cyclophosphamide
Cohort 2ExperimentalPatients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by young TIL and low Dose Aldesleukin (72,000 IU/Kg) IV every 8 hours for up to 12 doses
  • Aldesleukin
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        -  INCLUSION CRITERIA:

               1. Measurable metastatic (stage IV) or unresectable non-small cell lung cancer
                  (including but not limited to squamous cell carcinoma, adenosquamous carcinoma,
                  or adenocarcinomas) with at least one lesion that is resectable for TIL
                  generation. (Note: neuroendocrine tumors are not eligible.)

               2. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter
                  and asymptomatic are eligible. Lesions that have been treated with stereotactic
                  radiosurgery must be clinically stable for 1 month after treatment for the
                  patient to be eligible. Patients with surgically resected brain metastases are
                  eligible.

               3. Received at least one platinum-based chemotherapy regimen and at least one FDA
                  approved targeted treatment (when appropriate) and progressed.

               4. Clinical performance status of ECOG 0 or 1.

               5. Greater than or equal to 18 years of age and less than or equal to 70 years of
                  age.

               6. Patients of both genders must be willing to practice birth control from the time
                  of enrollment on this study and for four months after treatment.

               7. Willing to sign a durable power of attorney

               8. Able to understand and sign the Informed Consent Document

        I. Hematology:

          -  Absolute neutrophil count greater than 1000/mm3 without support of filgrastim

          -  Normal WBC (> 3000/mm3).

          -  Hemoglobin greater than 8.0 g/dl. Subjects may be transfused to reach this cut-off.

          -  Platelet count greater than 100,000/mm3

             j. Serology:

          -  Seronegative for HIV antibody. (The experimental treatment being evaluated in this
             protocol depends on an intact immune system. Patients who are HIV seropositive can
             have decreased immune competence and thus may be less responsive to the experimental
             treatment and more susceptible to its toxicities.)

          -  Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. If
             hepatitis C antibody test is positive, then patient must be tested for the presence
             of antigen by RTPCR and be HCV RNA negative.

             k. Chemistry:

          -  Serum ALT/AST less than 2.5 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 or equal to 3 mg/dl.

             l.Women of child-bearing potential must have a negative pregnancy test because of the

        potentially dangerous effects of the treatment on the fetus.

        m. More than four weeks must have elapsed since any prior systemic therapy at the time the
        patient receives the preparative regimen, and patients toxicities must have recovered to a
        grade 1 or less. Patients may have undergone minor surgical procedures or local
        radiotherapy within the past 4 weeks.

        n. More than two weeks must have elapsed since any prior palliation for major bronchial
        occlusion or bleeding at the time the patient receives the preparative regimen, and
        patient s toxicities must have recovered to a grade 1 or less.

        EXCLUSION CRITERIA:

          1. Women of child-bearing potential who are pregnant or breastfeeding because of the
             potentially dangerous effects of the treatment on the fetus or infant.

          2. Ongoing need for pharmacological immunosuppression, including steroids

          3. Active systemic infections, coagulation disorders or other active or uncompensated
             major medical illnesses of the cardiovascular, respiratory or immune system.

          4. Major bronchial occlusion or bleeding not amenable to palliation.

          5. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency

             Disease and AIDS).

          6. Concurrent 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.)

          7. History of severe immediate hypersensitivity reaction to any of the agents used in
             this study.

          8. Any patient known to have an LVEF less than or equal to 45%.

          9. Documented LVEF of less than or equal to 45% tested in patients with:

             -Clinically significant atrial and/or ventricular arrhythmias including but not
             limited to:

             atrial fibrillation, ventricular tachycardia, second or third degree heart block

             -Age (Bullet) 60 years old

         10. Documented FEV1 of less than or equal to 50% predicted in patients with clinical

             symptomatology.

         11. Any of the following will exclude patients from the high-dose aldesleukin arm, but
             may be eligible for the low-dose aldesleukin arm:

               -  Greater than 2 invasive thoracic procedures

               -  Poor exercise tolerance

               -  Greater than 66 years of age

         12. Clinically significant patient history which in the judgment of the Principal
             Investigator would compromise the patient s ability to tolerate high-dose.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the rate of tumor regression
Time Frame:Approximately 5 years
Safety Issue:
Description:Primary Completion Date: The date that the final subject will be examined or an intervention received for the purposes of final collection of data for the primary outcome.02/28/2020

Secondary Outcome Measures

Measure:To determine the phenotypic and functional characteristics of TIL derived from NSCLC.
Time Frame:approximately 5 years
Safety Issue:
Description:
Measure:To determine the toxicity of this treatment regimen.
Time Frame:approximately 5 years
Safety Issue:
Description:
Measure:To determine the feasibility of generating TIL from patients with NSCLC
Time Frame:approximately 5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • Metastatic
  • Non-Small Cell Lung Cancer
  • NSCLC
  • Lung Cancer

Last Updated

April 20, 2017