The Mechanism of Action of Chlormethine (CL) Gel in the Treatment of MF-CTCL Adult Patients

NCT06421571 | Recruiting DMC

• 1 other identifier: 441/05-08-2020
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Chlormethine is a topical alkylating agent whose role in MF-CTCL has been extensively studied over the last 40 years. While its efficacy is well established, many safety concerns have been raised due to high rates of delayed cutaneous hypersensitivity to aqueous solutions that limit the prolonged use of chlormethine in clinical practice. It has been shown that complete response to topical chlormethine is associated with lower risk of disease progression. Accordingly, clinical data from the investigators' clinic confirm that chlormethine gel is a safe and effective treatment, which be used in early and advanced stages of cutaneous lymphomas. Based investigators' clinical and biological results , the investigators like to further investigate the change in the percentage as well as the profile of malignant and inflammatory cells by CyTOF analysis and further investigate the pathways (eg OX40, PDL1) involved in this process.

Conditions

Mycosis Fungoides

Outcome Measures

Primary Outcomes (7)

• Clinical objectives: Number of participants with treatment-related adverse events as assessed by CTCAEv4.0.

  Number of participants with treatment-related adverse events as assessed by CTCAEv4.0.

  12 months

• Clinical objectives: Clinical response mSWAT

  Clinical response mSWAT (at least score ≥50% improvement from baseline) every month for the first three months, and every 3 months thereafter (at months 6, 9, 12), as per current clinical practice

  12 months

• Clinical objectives: Dermatitis occurrence

  Dermatitis occurrence (before any topical steroids application)

  12 months

• Biological objectives: Evaluation of the impact of chlormethine gel treatment on malignant and inflammatory cells

  Determine and compare immune cells vs malignant cells at single cell level

  12 months

• Biological objectives:Evaluation of the impact of chlormethine gel treatment exhibits on the profile of cytokines

  Evaluation of the impact of chlormethine gel treatment exhibits on the profile of Th1/Th2 cytokines (ELISA)

  12 months

• Biological objectives:Evaluation of the impact that CL gel treatment exerts on the major signaling pathways

  Evaluation of the impact that CL gel treatment exerts on the JAK/STAT, NF-κB AKT, MAP signaling pathways (Western Blotting)

  12 months

• Patient-Reported Outcomes

  Questionnaires of Quality of Life

  12 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

MF-CTCL patients, from outpatient PCL clinic from Attikon University Hospital, who will be candidates for topical treatment with chlormethine gel will be informed and invited to participate in this prospective data collection. All clinical and biological investigations (including blood samplings and biopsies) will be prescribed and arranged as part of standard routine clinical practice at PCL center.

You may qualify if:

• MF-CTCL early-stage diagnosed patients, or late-stage patients that relapse without current active tumoral disease who still have patches and/or plaques.
• Age ≥ 18 years
• Patients naïve from CL gel treatment
• Early-stage patients who will be using CL as monotherapy: at enrolment without any concomitant MF treatment
• Early-stage patients if treated with other topical or systemic (late or early-stage patients) at enrolment, then a 2 week for topical steroids (and/or other topical treatment) and 4 weeks for systemic treatments wash out period will be required
• Women of child bearing potential must have a negative serum pregnancy test within 3 days prior enrolment.
• Women of child bearing potential should use adequate birth control measures, during the study treatment period until 30 days after treatment
• Women who are breast feeding should discontinue nursing prior to the first application of study treatment and until 30 days after the last study treatment
• Before patient enrolment, written informed consent must be given according to ICH/GCP

You may not qualify if:

• Patients with multiple active tumors - progressive disease
• Patients with concomitant and chronic use of topical or systemic corticosteroids for the treatment of any other disease
• Patients treated with concomitant topical (except chlormethine gel) and/or systemic MF treatments who have missed the wash-out period (2 weeks for topical treatment and 4 weeks for systemic treatment)
• Acute flare or atopic dermatitis or other dermatosis in the last 3 weeks
• Pregnant and breast-feeding women
• Patients unable to comply with study procedures (e.g. provide written consent, fill in the questionnaires, geographical condition potentially hampering compliance with the study protocol and follow-up schedule).
• Known hypersensitivity to any component of the CL gel formulation
• Concurrent or planned local or systemic anti-CTCL therapies

Sponsors & Collaborators

• National and Kapodistrian University of Athens: lead
• RECORDATI GROUP: collaborator

Study Sites (1)

1 Rimini Street, ATTIKON University Hospital

Athens, 12462, Greece

RECRUITING

Related Publications (11)

• Inturi S, Tewari-Singh N, Agarwal C, White CW, Agarwal R. Activation of DNA damage repair pathways in response to nitrogen mustard-induced DNA damage and toxicity in skin keratinocytes. Mutat Res. 2014 May-Jun;763-764:53-63. doi: 10.1016/j.mrfmmm.2014.04.002. Epub 2014 Apr 13.

  PMID: 24732344 RESULT

• 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.

  PMID: 23069814 RESULT

• Kim EJ, Guitart J, Querfeld C, Girardi M, Musiek A, Akilov OE, Angello JT, Bailey WL, Geskin LJ. The PROVe Study: US Real-World Experience with Chlormethine/Mechlorethamine Gel in Combination with Other Therapies for Patients with Mycosis Fungoides Cutaneous T-Cell Lymphoma. Am J Clin Dermatol. 2021 May;22(3):407-414. doi: 10.1007/s40257-021-00591-x. Epub 2021 Mar 3.

  PMID: 33656660 RESULT

• Kim YH, Liu HL, Mraz-Gernhard S, Varghese A, Hoppe RT. Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol. 2003 Jul;139(7):857-66. doi: 10.1001/archderm.139.7.857.

  PMID: 12873880 RESULT

• 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.

  PMID: 12588222 RESULT

• Koumourtzis M, Lampadaki K, Dalamaga M, Papadavid E. Chlormethine Gel is Efficient and Safe in Mycosis Fungoides Skin Lesions. Acta Derm Venereol. 2022 Jun 9;102:adv00730. doi: 10.2340/actadv.v102.1095.

  PMID: 35199177 RESULT

• Lampadaki K, Koumourtzis M, Karagianni F, Marinos L, Papadavid E. Chlormethine Gel in Combination with Other Therapies in the Treatment of Patients with Mycosis Fungoides Cutaneous T Cell Lymphoma: Three Case Reports. Adv Ther. 2021 Jun;38(6):3455-3464. doi: 10.1007/s12325-021-01721-x. Epub 2021 Apr 30.

  PMID: 33928511 RESULT

• Papadavid E, Koumourtzis M, Nikolaou V, Lampadaki K, Marinos L, Patsatsi A, Georgiou E, Dalamaga M, Stratigos A. Chlormethine gel is effective for the treatment of skin lesions in patients with early- and late-stage mycosis fungoides in clinical practice. J Eur Acad Dermatol Venereol. 2022 Oct;36(10):1751-1757. doi: 10.1111/jdv.18183. Epub 2022 May 12.

  PMID: 35470483 RESULT

• Ramsay DL, Parnes RE, Dubin N. Response of mycosis fungoides to topical chemotherapy with mechlorethamine. Arch Dermatol. 1984 Dec;120(12):1585-90.

  PMID: 6508330 RESULT

• 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.

  PMID: 34091453 RESULT

• Pavlidis A, Karagianni F, Vetsika EK, Koumourtzis M, Lampadaki K, Piperi C, Pappa V, Papadavid E. Bio-P-10 - Evaluation of the role of different cell populations in mycosis fungoides microenvironment as a tool for biomarker identification for disease progression and individualized therapy. EJC 2021:156(S1);S40-S41

  RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Skin biopsies and blood from MF-CTCL patients

MeSH Terms

Conditions

Mycosis Fungoides

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 26, 2024
• First Posted: May 20, 2024
• Study Start: February 21, 2023
• Primary Completion: February 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 20, 2024

Record last verified: 2024-05

Locations

GR (1)