T Cell Receptor Immunotherapy for 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
This study is testing a new treatment for advanced lung cancer that uses special immune cells from patients' own tumors to see if it can help shrink their cancer.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 85 (estimated) |
| Ages | 18 Years to 72 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | chemotherapy, cyclophosphamide, fludarabine |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT02133196 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates an experimental therapy that utilizes tumor infiltrating lymphocytes (TIL) derived from patients' own tumors to treat metastatic non-small cell lung cancer (NSCLC). The approach involves selecting and expanding specific white blood cells believed to be effective against the tumor, followed by their reinfusion into the patient after a preparative regimen. The study aims to assess the safety and efficacy of this treatment in inducing tumor regression in patients with advanced NSCLC. Participants will undergo a thorough evaluation at the NIH Clinical Center to determine eligibility and treatment feasibility.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18-72 with measurable metastatic non-small cell lung cancer and at least one resectable tumor lesion.
Not a fit: Patients with neuroendocrine tumors or those who have not progressed after first-line systemic therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could provide a new, effective treatment option for patients with advanced non-small cell lung cancer.
How similar studies have performed: Other studies using tumor infiltrating lymphocytes in melanoma have shown promising results, suggesting potential success for this approach in NSCLC.
Eligibility criteria
Show full inclusion / exclusion 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. Age \>= 18 years of age and \<= 72 years of age.
6. Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and for 12 months after the last dose of combined chemotherapy for individuals of childbearing potential (IOCBP) and for four months after treatment for individuals able to father a child.
7. Willing to sign a durable power of attorney
8. Able to understand and sign the Informed Consent Document
I. Hematology:
* Absolute neutrophil count \> 1000/mm\^3 without support of filgrastim
* Normal WBC (\>= 2500/mm\^3).
* Hemoglobin \> 8.0 g/dl. Subjects may be transfused to reach this cut-off.
* Platelet count \>= 80,000/mm\^3
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 RT-PCR and be HCV RNA negative.
k. Chemistry:
* Serum ALT/AST \<= 2.5 times the upper limit of normal.
* Serum creatinine \<= 1.6 mg/dl.
* Total bilirubin \<= 2 mg/dl, except in patients with Gilbert's Syndrome, who must have a total bilirubin \<= 3 mg/dl.
l. IOCBP must have a negative pregnancy test or evidence that they are not pregnant (e.g., ultrasound or serial HCG measurements) prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.
m. Patients must have completed any prior systemic therapy at the time of enrollment.
Note: Patients may have undergone minor surgical procedures or local radiotherapy within the past 4 weeks, as long as related major organ toxicities have recovered to grade 1 or less.
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. Participants who are nursing because of the potentially dangerous effects of the treatment on the 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. For select patients with a clinical history prompting cardiac evaluation: last known LVEF \<= 45%.
9. For select patients with a clinical history prompting pulmonary evaluation: known FEV1 \<= 50%
10. 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
* Clinically significant patient history which in the judgment of the Principal Investigator would compromise the patient s ability to tolerate high-dose.
11. Patients who are receiving any other investigational agents.
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: James C Yang, M.D. — National Cancer Institute (NCI)
- Study coordinator: NCI SB Immunotherapy Recruitment Center
- Email: irc@nih.gov
- Phone: (866) 820-4505
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.