Circadian-Optimized Light Therapy for the Treatment of Patients With Advanced Melanoma Receiving Tumor-Infiltrating Lymphocyte Therapy

PRIMARY OBJECTIVE:

I. Evaluate the feasibility of COLT with TIL therapy.

SECONDARY OBJECTIVES:

I. Evaluate the safety of COLT with TIL therapy. II. Evaluate the acceptability of COLT intervention to patients. III. Evaluate the effect of COLT on patient-reported quality of life metrics.

EXPLORATORY OBJECTIVES:

I. Evaluate changes that occur in patient circadian clocks with COLT during TIL therapy using actigraphy and circadian clock gene analysis.

II. Evaluate the alterations and time course that occur in tumor immune cell subsets and phenotype with COLT during TIL therapy.

III. Evaluate the toxicities related to TIL therapy (i.e., cytopenia, interleukin 2 [IL-2] toxicity) that occur with COLT during TIL therapy.

OUTLINE:

Starting on day -14, patients receive access to the Circadian OS application and within the first hour of waking up undergo light therapy sessions over 1 hour daily between 8:00 and 10:00 am for up to 28 days after TIL in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care TIL infusion on day 0. Patients may optionally continue COLT for up to 90 days post TIL infusion. Patients also wear wrist actigraphy continuously to monitor sleep-wake cycles, light exposure, and circadian rhythms during TIL therapy. Additionally, patients undergo blood sample collection throughout the study.

After completion of study intervention, patients are followed up at 30 days.

Inclusion criteria

• Documented informed consent of the participant and/or legally authorized representative
• Age: ≥ 18 years
• Ability to read and understand English for questionnaires
• Progression on or after immune checkpoint inhibitor therapy
• Deemed eligible and consented for standard-of-care TIL therapy (lifileucel/Amtagvi)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (typically required for TIL therapy; confirm with clinical standards of practice [SOP])

Exclusion criteria

• Explicit Munich Chronotype Questionnaire (MCTQ) cutoffs (< 2:00, > 5:00)
• Use of melatonin or pharmacologic sleep aids (e.g., zolpidem, trazodone, benzodiazepines) within 14 days prior to enrollment
• Night shift work within the past 30 days or expected during the intervention
• Travel across ≥ 2 time zones within the past 14 days
• Diagnosed or suspected untreated moderate to severe obstructive sleep apnea
• History of mania, hypomania, bipolar disorder, migraine (with or without photophobia), or active seizure disorder
• Active psychosis, suicidal ideation, or recent psychiatric hospitalization (< 3 months)
• Ocular conditions exacerbated by bright light exposure
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)