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

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ClinicalTrials.gov Identifier: NCT02133196
Recruitment Status : Recruiting
First Posted : May 7, 2014
Last Update Posted : November 6, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief 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 18-70 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.


Condition or disease Intervention/treatment Phase
Advanced Non-Small Cell Lung Cancer Squamous Cell Carcinoma Advanced NSCLC Adenosquamous Carcinoma Adenocarcinomas Drug: Aldesleukin Drug: Fludarabine Drug: Cyclophosphamide Biological: Young TIL Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 85 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 17, 2014
Estimated Primary Completion Date : October 23, 2024
Estimated Study Completion Date : October 23, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Aldesleukin

Arm Intervention/treatment
Experimental: Arm 1/High-Dose Aldesleukin
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine plus young TIL plus high-dose Aldesleukin
Drug: Aldesleukin
Aldesleukin at 720,000 (Arm 1) or 72,000 (Arm 2) IU/kg IV based on total body weight) over 15 minutes approximately every eight hours (+/- 1hr) 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
On day 0, TIL will be infused intravenously (IV) on the Patient Care Unit over 20 to 30 minutes.

Experimental: Arm 2/Low-Dose Aldesleukin
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine plus young TIL plus low-dose Aldesleukin
Drug: Aldesleukin
Aldesleukin at 720,000 (Arm 1) or 72,000 (Arm 2) IU/kg IV based on total body weight) over 15 minutes approximately every eight hours (+/- 1hr) 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
On day 0, TIL will be infused intravenously (IV) on the Patient Care Unit over 20 to 30 minutes.




Primary Outcome Measures :
  1. Response rate [ Time Frame: 6 and 12 weeks after cell infusion, then every 3 months x3, every 6 months x2 years, then PI discretion ]
    Percentage of patients who have a clinical response to treatment (objective tumor regression)


Secondary Outcome Measures :
  1. Phenotypic and functional characteristics of TIL. [ Time Frame: 2-4 years post cell infusion ]
    Find in vitro characteristics of the infused cells which correlate with in vivo antitumor activity. Evaluation of the activity, specificity, and telomere length of infused TIL.

  2. Frequency of treatment related adverse events. [ Time Frame: 30 days after end of treatment ]
    Aggregate of all adverse events and their frequency and severity

  3. Feasibility of generating TIL from patients with NSCLC [ Time Frame: 3-6 months post cell harvest ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. All patients must have had at least one appropriate first line systemic therapy 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.

o. Subjects must be co-enrolled in protocol 03-C-0277

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 (e.g.: requiring anti-infective treatment), coagulation disorders or any other active or uncompensated major medical illnesses.
  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 or have a history of ischemic heart disease, chest pain

    -Age greater than or equal to 65 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.
  13. Patients who are receiving any other investigational agents.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02133196


Contacts
Contact: Mary E. Link, R.N. (866) 820-4505 IRC@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center    866-820-4505    irc@nih.gov   
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: James C Yang, M.D. National Cancer Institute (NCI)

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02133196     History of Changes
Other Study ID Numbers: 140104
14-C-0104
First Posted: May 7, 2014    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 1, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Metastatic
Non-Small Cell Lung Cancer
NSCLC
Lung Cancer

Additional relevant MeSH terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Adenocarcinoma
Carcinoma, Adenosquamous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Squamous Cell
Neoplasms, Complex and Mixed
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Aldesleukin
Interleukin-2
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents