Safety and Efficacy of Nitrogen Mustard in Treatment of Mycosis Fungoides

A Phase II Pivotal Trial to Evaluate the Safety and Efficacy of Nitrogen Mustard (NM) 0.02% Ointment Formulations in Patients With Stage I or IIA Mycosis Fungoides (MF)

This study will evaluate the efficacy, tolerability and safety of the topical application of mechlorethamine (MCH) formulations in patients with stage I or IIA mycosis fungoides (MF).

Study Overview

• Status: Completed
• Conditions: Mycosis Fungoides
• Intervention / Treatment: Drug: mechlorethamine-MCH (nitrogen mustard)

Detailed Description

The successful use of mechlorethamine (MCH) as a topical agent in the treatment of mycosis fungoides, a form of cutaneous T-cell lymphoma, was first reported in the late 1950s, and provided a rationale for skin-directed chemotherapy that minimized systemic toxicity. Since then, multiple investigators have demonstrated the safety and efficacy of topically applied MCH in the treatment of mycosis fungoides. This study will evaluate the efficacy (non-inferiority), tolerability and safety of topical application of MCH proprietary gel versus a compounded ointment formulation in Aquaphor in patients with stage I or IIA MF.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 61611
      • Northwestern University - Dept. of Dermatology
  • New York
    • New York, New York, United States, 10016
      • NYU Medical Center Dept. of Dermatology
    • New York, New York, United States, 10032
      • Columbia University, Dept. of Dermatology
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Oklahoma University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas, Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas, M.D. Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Utah Clinical Trials, LLC
  • Wisconsin
    • Madison, Wisconsin, United States, 53791
      • University Of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients with mycosis fungoides confirmed by a skin biopsy
• Stage I or IIA patients must have been treated previously with prior topical therapies including PUVA, UVB, topical steroids, but not NM within the past 2 years, or topical carmustine (BCNU)
• Patients must be otherwise healthy with acceptable organ function.
• Prior to initiating study therapy, patients must not have had topical therapy within four weeks
• Lab values within normal range
• Willing/able to give consent
• Must use effective means of contraception if of childbearing potential

Exclusion Criteria:

• Newly diagnosed mycosis fungoides with no prior therapy
• A prior history of treatment with topical NM within the past 2 years or topical carmustine (BCNU)
• Use of topical or systemic therapies for MF within four (4) weeks of entry in the study
• Patients with a diagnosis of stage IIB-IV MF
• Serious known concurrent medical illness or infection, which could potentially present a safety risk and/or prevent compliance with the requirements of the treatment program
• Pregnant or nursing females, or males and females of childbearing potential, not using an effective means of contraception
• Patients who have had radiation therapy within one year of study start
• Patients who have a history of a higher T score than T2 or a higher N score than N1
• Patients who do not agree to do all labs at one site

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1 (PG - NM (MCH) 0.02%); PG - mechlorethamine-MCH (nitrogen mustard) 0.02% gel To evaluate the tolerability and safety of topical mechlorethamine-MCH (nitrogen mustard) 0.02% ointment formulations in patients with stage I or IIA MF	Drug: mechlorethamine-MCH (nitrogen mustard); All affected areas (lesions) are to be treated once daily for twelve months with mechlorethamine-MCH (nitrogen mustard) 0.02% PG or NM 0.02% AP ointment; Other Names: mechlorethamine; nitrogen mustard
Active Comparator: 2 (AP - MCH(NM) 0.02%); AP - mechlorethamine-MCH (nitrogen mustard) 0.02% compounded in Aquaphor To evaluate the tolerability and safety of mechlorethamine-MCH (nitrogen mustard)0.02% ointment formulations in patients with stage I or IIA MF	Drug: mechlorethamine-MCH (nitrogen mustard); All affected areas (lesions) are to be treated once daily for twelve months with mechlorethamine-MCH (nitrogen mustard) 0.02% PG or NM 0.02% AP ointment; Other Names: mechlorethamine; nitrogen mustard

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of Response Rates Based on CAILS	The ratio of the response rate of the patients treated with the PG formulation to the response rate of the patients treated with the AP formulation. Skin response determined by at least a 50% reduction from baseline in the Composite Assessment of Index Lesion Severity (CAILS) following up to 12 months of treatment	Assessment made at Day 1 and every subsequent visit during treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity-weighted Assessment Tool (SWAT) Within up to 12 Months by 2 or More Consecutive Observations Over at Least 4 Weeks		Assessment made at Day 1 and every subsequent visit during treatment
Percent of Participants Achieving at Least 50% Improvement of Severity Weighted Assessment Tool (SWAT)	Assessment of lesion distribution and severity. A responder analysis was performed on whether subject achieved at least 50% improvement on scale. This had to be confirmed on at least one visit at least 4 weeks apart.	Baseline to end of therapy

Collaborators and Investigators

• Sponsor: Yaupon Therapeutics
• Investigators: Study Director: Stuart Lessin, M.D., Fox Chase Cancer Center

Publications and helpful links

General Publications

• Kim YH, Martinez G, Varghese A, Hoppe RT. Topical nitrogen mustard in the management of mycosis fungoides: update of the Stanford experience. Arch Dermatol. 2003 Feb;139(2):165-73. doi: 10.1001/archderm.139.2.165.
• Kim YH. Management with topical nitrogen mustard in mycosis fungoides. Dermatol Ther. 2003;16(4):288-98. doi: 10.1111/j.1396-0296.2003.01640.x.
• Kim YH, Jensen RA, Watanabe GL, Varghese A, Hoppe RT. Clinical stage IA (limited patch and plaque) mycosis fungoides. A long-term outcome analysis. Arch Dermatol. 1996 Nov;132(11):1309-13.
• Querfeld C, Scarisbrick JJ, Assaf C, Kim YH, Guitart J, Quaglino P, Hodak E. Chlormethine Gel Versus Chlormethine Ointment for Treatment of Patients with Mycosis Fungoides: A Post-Hoc Analysis of Clinical Trial Data. Am J Clin Dermatol. 2022 Jul;23(4):561-570. doi: 10.1007/s40257-022-00687-y. Epub 2022 May 10.
• Querfeld C, Scarisbrick JJ, Assaf C, Guenova E, Bagot M, Ortiz-Romero PL, Quaglino P, Bonizzoni E, Hodak E. Post hoc Analysis of a Randomized, Controlled, Phase 2 Study to Assess Response Rates with Chlormethine/Mechlorethamine Gel in Patients with Stage IA-IIA Mycosis Fungoides. Dermatology. 2022;238(2):347-357. doi: 10.1159/000516138. Epub 2021 Jun 4.
• Lessin SR, Duvic M, Guitart J, Pandya AG, Strober BE, Olsen EA, Hull CM, Knobler EH, Rook AH, Kim EJ, Naylor MF, Adelson DM, Kimball AB, Wood GS, Sundram U, Wu H, Kim YH. Topical chemotherapy in cutaneous T-cell lymphoma: positive results of a randomized, controlled, multicenter trial testing the efficacy and safety of a novel mechlorethamine, 0.02%, gel in mycosis fungoides. JAMA Dermatol. 2013 Jan;149(1):25-32. doi: 10.1001/2013.jamadermatol.541.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: September 7, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 14, 2005

Study Record Updates

• Last Update Posted (Estimate): October 31, 2012
• Last Update Submitted That Met QC Criteria: October 2, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Mycosis Fungoides; Nitrogen Mustard; Cutaneous T-Cell Lymphoma; CTCL - Mycosis Fungoides
• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Mechlorethamine; Nitrogen Mustard Compounds
• Other Study ID Numbers: 2005NMMF-201-US