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

A Single-Center, Prospective Pilot Trial of Circadian-Optimized Light Therapy (COLT) in Patients Undergoing Tumor-Infiltrating Lymphocyte (TIL) Therapy for Metastatic Melanoma

This phase I trial tests the effect of Circadian-Optimized Light Therapy (COLT) in conjunction with standard of care tumor-infiltrating lymphocytes (TIL) therapy in treating patients with melanoma that may have spread from where it first started to nearby tissue, lymph nodes or distant parts of the body (advanced). Circadian rhythm is the body's natural 24 hour clock which helps keep the body operating on a healthy wake-sleep cycle. Exposure to morning light has been shown to have a positive impact. Patients with advanced cancers often experience circadian disruption, including exposure to hospital-related light, treatment side effects, and inflammation. TIL are made by collecting and growing specialized T cells (a type of white blood cell) from a patient's tumor and given back to the patient to help stimulate the immune system in different ways to stop tumor cells from growing. However, disruptions in the circadian rhythm may impact the effectiveness of TIL therapy. COLT is a home-based digital intervention that delivers circadian-effective morning light using the Circadian OS iPad application. Daily light exposure may help prevent circadian disruption and improve immune and inflammatory responses. Adding COLT sessions to standard of care therapy with TIL may be safe and tolerable in patients with advanced melanoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Cutaneous Melanoma; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Advanced Cutaneous Melanoma
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Biospecimen Collection; Other: Internet-Based Intervention; Other: Medical Device Usage and Evaluation; Procedure: Phototherapy; Biological: Therapeutic Tumor Infiltrating Lymphocytes

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
      • Principal Investigator: Kelly Mahuron
      • Contact: Kelly Mahuron; Email: kmahuron@coh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (COLT, TIL); 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.

Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Other: Internet-Based Intervention; Receive access to Circadian OS application; Other: Medical Device Usage and Evaluation; Wear wrist actigraphy; Procedure: Phototherapy; Undergo light therapy sessions; Other Names: Bright Light Therapy; light therapy; Actinotherapy; Biological: Therapeutic Tumor Infiltrating Lymphocytes; Given infusion; Other Names: Tumor Infiltrating Lymphocytes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence	Will be measured as the proportion of prescribed daily Circadian-Optimized Light Therapy (COLT) sessions attempted by each participant. Session initiation, duration, and completion will be automatically recorded by the Circadian OS application and verified at scheduled study visits. Participants who attempt at least 50% of sessions will be considered adherent. Adherence data will be summarized descriptively, including the median and range of completion rates across participants. Will be reported with a two-sided 95% exact (Clopper-Pearson) confidence interval.	From the start of intervention through the end of the intervention period, assessed up to day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity, and attribution of COLT-related treatment-emergent adverse events	Will be graded by Common Terminology Criteria for Adverse Events version 5.0.	From the first day of COLT administration through 30 days after completion of intervention
Patient-reported acceptability and usability of COLT	Will be assessed using the Acceptability of Intervention Measure questionnaire. Responses will be summarized as total and subscale scores with means, standard deviations, medians, and ranges. The proportion of participants meeting a predefined threshold for acceptability or usability on the instrument's scale will also be reported with exact 95 percent confidence intervals.	Up to day 90
Patient scores for quality of life and symptom burden	Will be assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care. Data will be evaluated for functional scale, global health status, and symptoms. Scores will be summarized descriptively and compared across study phases.	Up to day 90
Patient scores for fatigue	Will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire. Data will be evaluated for functional scale, global health status, and symptoms. Scores will be summarized descriptively and compared across study phases.	Up to day 28
Patient scores for depression	Will be evaluated using PROMIS Depression questionnaire. Data will be evaluated for functional scale, global health status, and symptoms. Scores will be summarized descriptively and compared across study phases.	Up to day 90

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Kelly Mahuron, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): December 23, 2026
• Primary Completion (Estimated): July 5, 2027
• Study Completion (Estimated): July 5, 2027

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Phototherapy; Ultraviolet Therapy
• Other Study ID Numbers: 25102 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2026-03733 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No