Skip to main content

Autologous Tumor Infiltrating Lymphocytes and High-Dose Interleukin 2 for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Cancer or Stage III-IV Cutaneous or Mucosal Melanoma

Trial Status: Active

This phase I trial studies the possible benefits and / or side effects of autologous tumor infiltrating lymphocytes and high-dose IL-2 in treating patients with head and neck squamous cell cancer that has come back (recurrent) or has spread to other places in the body (metastatic) or stage III-IV cutaneous or mucosal melanoma. Autologous tumor infiltrating lymphocytes are special tumor-fighting cells that are taken from patients’ tumors, grown in the laboratory, and then given back to the patient to fight their cancer. High-dose IL-2 increases the activity and growth of white blood cells called T lymphocytes and B lymphocytes. Giving autologous tumor infiltrating lymphocytes and high-dose IL-2 may kill more cancer cells and help researchers learn more about the transfer of autologous tumor infiltrating lymphocytes to treat cancer.

Inclusion Criteria

  • Patient has the ability to understand and the willingness to sign a written informed consent
  • Patients with a histologically confirmed diagnosis of head and neck squamous cell carcinoma OR metastatic cutaneous or mucosal melanoma measurable per Response Evaluation Criteria in Solid Tumors (RECIST)
  • Progressive squamous cell cancer of the head and neck or metastatic melanoma since prior systemic treatment and who are: * Not candidates for known curative intent therapy * Progressed following at least one prior systemic therapy ** Unresectable metastatic melanoma: must have progressed on pembrolizumab, nivolumab, or the combination of nivolumab and ipilimumab prior to enrollment ** Unresectable BRAF V600E-mutated metastatic melanoma: must have progressed on pembrolizumab, nivolumab, or the combination of nivolumab and ipilimumab prior to enrollment. In addition, must have progressed on (or been intolerant to) prior BRAF-targeting therapy (with or without a MEK inhibitor) prior to enrollment ** Recurrent/metastatic squamous cell cancer of the head and neck: must have received prior therapy with a platinum-containing regimen and with pembrolizumab or nivolumab prior to enrollment * Have advanced disease ** Melanoma = unresectable stage III or stage IV ** Head and neck = recurrent or metastatic disease
  • Patient has undergone resection and a successful generation of an autologous TIL culture (per Human Research Protections Program [HRPP] 190787)
  • Patient with up to three brain lesions may be included if the lesions are < 1 cm and demonstrate radiographic stability for at least three months following therapy
  • Patient is >= 18 years of age
  • Patient has a life expectancy of greater than 3 months
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Absolute neutrophil count >= 1.0 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 9.0 g/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Calculated creatinine clearance (estimated glomerular filtration rate [eGFR]) > 50 ml/min
  • Total bilirubin =< 1.5 mg/dl (or =< 3 mg/dl in patients with Gilbert’s syndrome)
  • Patient is seronegative for human immunodeficiency virus (HIV) antibody * Note: The experimental treatment being evaluated depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities
  • Patient is seronegative for hepatitis B antigen, or hepatitis C antibody or antigen
  • Patient agrees to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study treatment, and for 4 months after receiving all protocol related therapy
  • More than four weeks has elapsed since the patient received any prior systemic therapy at the time of enrollment. Patients must have stable or progressing disease after prior treatment * Note: Patient may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities from surgery have recovered to grade 1 or less
  • Patient has recovered to =< grade 1 or baseline from adverse events due to prior therapy
  • Patient has stable or progressing disease after at least one prior treatment
  • Six weeks or more have elapsed since the patient received any prior anti-CTLA4 antibody therapy to allow antibody levels to decline * Note: If patient has previously received ipilimumab or tremelimumab, anti-PD1 or anti-PD-L1 antibodies, and have documented gastrointestinal (GI) toxicity, the patient must have completely recovered to baseline and more than six weeks off steroid therapy
  • A subset of head and neck squamous cell carcinoma subjects (N =< 5) will have the TIL product labeled with CS-1000. Subjects in this subset must meet the additional eligibility criteria below: * Patients with neck recurrence should have solid (rather than cystic) masses below the angle of the mandible (e.g. levels 3-5) * No evidence of hepatic metastases

Exclusion Criteria

  • Patient is currently using investigational agents
  • Patient had prior cell transfer therapy which included a non-myeloablative or myeloablative chemotherapy regimen
  • Patient is a female of child-bearing potential who is pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant
  • Patient requires immune suppressive therapy including but not limited to greater than physiologic steroid replacement
  • 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
  • Patient has any form of primary immunodeficiency (such as severe combined immunodeficiency disease and acquired immunodeficiency syndrome [AIDS])
  • Patient has opportunistic infections
  • Patient has a history of severe immediate hypersensitivity reaction to any of the agents used in this study
  • Patient has a history of coronary revascularization or ischemic symptoms
  • Patient is known to have an left ventricular ejection fraction (LVEF) =< 45%
  • Patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
  • Patient has documented forced expiratory volume in one second (FEV1) =< 60% predicted
  • Patient with untreated brain metastases


San Diego
University of California San Diego
Status: ACTIVE
Contact: Gregory Aram Daniels
Phone: 858-534-3804


I. To determine the rate of dose limiting toxicity of adoptive cell transfer (ACT) using cultured autologous tumor infiltrating lymphocytes (TIL) following non-myeloablative chemotherapy plus aldesleukin (IL-2) treatment for treating patients with cancer.


I. To provide preliminary evidence of efficacy.

II. To describe treatment related adverse events and to assess tolerability.

III. To describe the response rate and progression free survival in head and neck cancer and melanoma patients receiving ACT plus IL-2.

IV. To characterize immunologic changes during therapy including distribution of TILs after infusion.


LYMPHODEPLETION: Patients receive cyclophosphamide intravenously (IV) on days -8 and -7 and fludarabine phosphate IV on days -6 to -2.

TRANSPLANT: Patients receive autologous TIL IV over 20-30 minutes on day 0 (1-3 days after the last dose of lymphodepletion).

Between 3-24 hours after cell infusion, patients receive high-dose IL-2 IV over 15 minutes every 8 hours (q8h) for up to 5 days (maximum of 15 doses).

All treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 and 12 weeks, every 3 months for 9 months, and then every 6 months for 5 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of California San Diego

Principal Investigator
Gregory Aram Daniels

  • Primary ID 160710
  • Secondary IDs NCI-2020-14066
  • ID NCT03991741