Combining Topical Imiquimod With Local Radiotherapy for Treatment of Mycosis Fungoides

Mycosis fungoides (MF) is the most common subtype of cutaneous T cell lymphoma (MF) and presents as cutaneous patches, plaques, and tumors. Radiation therapy (RT) is a frequently pursued management option for CTCL, especially in patients with more advanced skin disease. Imiquimod stimulates a Th1 lymphocyte response with increased IL-2 and IFN-α, but also induces IFN-α, TNF-α, IL-1α, IL-6, and IL-8, thereby bridging both innate and adaptive immunity. Dosing of both radiotherapy (RT) and imiquimod are based on standard-of-care doses/frequencies for CTCL. The reason imiquimod topical is given for a week before giving RT is to prime innate immune activity for when RT is delivered. It is believed that this serves as an adjuvant for the CD8+ antitumor response generated by RT. The primary aim of this study is to assess the safety and efficacy of a combination local radiotherapy and topical imiquimod approach for the treatment of conventional (CD4+) MF.

Study Overview

• Status: Recruiting
• Conditions: Mycosis Fungoides
• Intervention / Treatment: Drug: Imiquimod; Radiation: Radiation Therapy

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Dermatology Clinical Trials Unit; Phone Number: 312-503-5944; Email: NUderm-research@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University Department of Dermatology
      • Contact: Dermatology CTU

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients must have confirmed stage IA-IIB mycosis fungoides.
• Patients must be 18-90 years of age.
• Patients must have failed at least one standard therapy for MF.
• Patients must have active, but stable disease for >6 months.
• Patients must have 4 or more discrete MF lesions with at least 2 of them with minimum combined surface area of >50cm2.
• POCBP must have a negative pregnancy test prior to registration on study.
• Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who are on current systemic or topical CTCL therapy, unless stable on the treatment for >6 months.
• Patients who have received antibiotic therapy within 4 weeks of study enrollment.
• Patients who are pregnant or nursing. Pregnant people are excluded from this study because IMQ is an agent with potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the gestational parent with IMQ, breastfeeding should be discontinued if the parent is treated with IMQ.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements.

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: Topical IMQ and localized RT; After the initial study visit, patients will immediately begin use of imiquimod cream at designated lesions (those with combined size >50cm2) nightly for 5 consecutive days a week over 6 weeks. One week into the imiquimod treatment course, radiation therapy will be administered at Northwestern Medicine by radiation oncologists familiar with MF in 2 fractions of 4 Gy (total 8 Gy) over 2 days to the same designated lesions.

Drug: Imiquimod; 5% cream applied topically 5 days/week for 6 weeks; Radiation: Radiation Therapy; 2 fractions of 4 Gys (total of 8 Gys) starting 1 week after Imiquimoid course over 2 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of a combination local radiotherapy and topical imiquimod approach for the treatment of conventional (CD4+) MF as measured by mSWAT at week 8.	The primary efficacy endpoint will be skin disease response as measured by mSWAT (Modified Severity-Weighted Assessment Tool) at week 8.	8 weeks
Incidence of treatment-emergent adverse events (safety and tolerability) of a combination local radiotherapy and topical imiquimod approach for the treatment of conventional (CD4+) MF.	Adverse event occurrence during study.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiome alterations before and after treatment	To measure alterations in lesional (tumor-associated) skin, nasal, and gut microbiomes before and after combination RT/imiquimod treatment and associate these differences in microbiomes with clinical response (and any toxicity). Differences in microbiome bacterial species will be measured by alpha and beta diversity metrics. Alpha diversity quantifies within sample diversity. Beta diversity compares between sample diversity (before and after treatment).	12 weeks
Tumor-associated and serum immune alterations before and after treatment	To correlate quantitative changes in tumor-associated and serum immune response profiles with clinical response to RT/imiquimod treatment (and any toxicity).	12 weeks

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Alan Zhou, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: April 29, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Bacterial Infections and Mycoses; Lymphoma; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Mycoses; Mycosis Fungoides; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Toll-Like Receptor Agonists; Immunomodulating Agents; Imiquimod
• Other Study ID Numbers: AZ10312022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No