Bexarotene and Ultra-Low Dose Total Skin Electron Beam Radiation Therapy for the Treatment of Mycosis Fungoides

PRIMARY OBJECTIVE:

I. To assess the safety at 1-month post-TSEB (day 52 of treatment) as defined by number of patients who develop Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 5, grade 3+ toxicities at 1 month post-treatment.

SECONDARY OBJECTIVES:

I. To determine the overall proportion of patients who develop CTCAE v.5, grade 3+ radiation dermatitis at 1 month post-treatment (day 52).

II. To determine overall skin response rate at 1 month post-TSEB (day 52) and 2 months post-TSEB (day 82) using the Modified Severity Weighted Assessment Tool (mSWAT).

III. To determine the proportion of patients who have best skin response at 1 month post-TSEB (day 52) and 2 months (day 82) post-TSEB using the mSWAT.

IV. To determine the proportion of patients who have ongoing complete response (CR) or partial response (PR) at 12 months after study initiation.

V. To determine the proportion of patients who require additional cycles of ultra-low dose TSEB beyond the first 4 Gy.

VI. To assess event-free survival from the start of standard dose bexarotene (300 mg day 15), which includes either progression of disease as defined as progressive disease on global response score, increased bexarotene dose above 300 mg, therapeutic switch, or delivery of additional radiotherapy after the completion of the TSEB cycles delivered as part of this protocol.

VII. To determine the proportion of patients who require continued antipruritic agents.

EXPLORATORY OBJECTIVES:

I. To assess the feasibility of using the Composite Assessment of Index Lesion Severity (CAILS) to assess response of a single index lesion by assessing concordance between the mSWAT (gold standard skin assessment tool) and CAILS index lesion assessments.

II. To assess patient-reported changes in quality of life (QoL) using questionnaires at start of TSEB treatment, 1 month (day 52), 2 months (day 82), 6 months (day 202), and 12 months (day 404) post treatment using European Quality of Life Five Dimension (EQ-5D), Functional Assessment of Cancer Therapy (FACT)-Lymphoma, Skindex-29, and assessment of pruritis intensity numerical rating scale.

III. To assess changes in cytokine levels from TSEB cycle 1 (day 15) to 2 weeks (day 37) and 2 months (day 82) post TSEB.

OUTLINE:

Patients receive bexarotene orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity. Patients undergo TSEB radiation therapy on days 22 and 23. Patients who have insufficient skin clearing may repeat cycles of TSEB radiation therapy on days 82, 112, 142, 172, and 202 in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples at baseline, and days 15, 37, and 82 and skin biopsy at baseline, days 15 and 37. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT at baseline and day 82.

After completion of study treatment, patients are followed up within 28 days, every 3 months for 1 year, and then every 3-6 months for 1 year.