Valchlor (mechlorethamine gel)

P=N/A, N=70, Recruiting, Columbia University | Trial completion date: Jul 2024 --> Aug 2026 | Trial primary completion date: Jul 2024 --> Aug 2026

P2, N=10, Completed, Soligenix | Recruiting --> Completed

P=N/A, N=40, Recruiting, National and Kapodistrian University of Athens

P2, N=10, Recruiting, Soligenix | Not yet recruiting --> Recruiting

P2, N=10, Not yet recruiting, Soligenix

In this exploratory, open-label, deep phenotyping trial a total of 21 early-stage (IA – IIA) MF patients were treated with chlormethine gel 160μg/g QD for 16 weeks...We show for the first time the feasibility of suction blister fluid analysis to investigate TME in MF patients. These results suggest that CD8+HLA-DR+ cytotoxic and regulatory T-lymphocytes have a prominent role in disease improvement with chlormethine therapy in MF.

Materials & In this exploratory, open-label, deep phenotyping trial a total of 21 early-stage (IA – IIA) MF patients were treated with chlormethine gel 160µg/g QD for 16 weeks... We show for the first time the feasibility of suction blister fluid analysis to investigate TME in MF patients. These results suggest that CD8+HLA-DR+ cytotoxic and regulatory T-lymphocytes have a prominent role in disease improvement with chlormethine therapy in MF.

P2, N=2, Terminated, European Organisation for Research and Treatment of Cancer - EORTC | N=100 --> 2 | Trial completion date: May 2028 --> Apr 2023 | Recruiting --> Terminated | Trial primary completion date: May 2025 --> Apr 2023; After an extensive assessment of the study feasibility, it was decided to discontinue the clinical trial due to poor recruitment.

Chlormethine (CL), also known as mechlorethamine, chlorethazine, mustine, HN2, caryolysine and embichin, is a synthetic deoxyribonucleic acid-alkylating agent that was used as a chemical weapon (mustard gas) during the First World War. CL has since been developed as a topical treatment for MF and prescribed as such for over 70 years. This review aims to summarize the current knowledge regarding the mechanism of action of CL in the cutaneous micro-environment, in the specific context of MF treatment.

LyP treatment options include topical steroids, topical bexarotene, phototherapy, nitrogen mustard, methotrexate, and intralesional interferon. In our patient, the papules and ulcerated plaques regressed under treatment with methotrexate

Most of the reported cases of squamous cell carcinoma (SCC) in patients with MF have been described following treatment with skin-directed therapies, including topical nitrogen mustard, total skin electron beam radiation, psoralen and ultraviolet A (PUVA) treatment, and narrow-band ultraviolet B (NBUVB) therapy...She was commenced on intravenous fluorouracil and cisplatin chemotherapy...KEY MESSAGE: This case highlighted that not all tumors that arise in patients with mycosis fungoides are tumor stage MF. SCC should be one of the differential diagnoses, especially in patients with a history of prolonged phototherapy in the past.

P=N/A, N=70, Recruiting, Columbia University | Trial completion date: Aug 2023 --> Jul 2024 | Trial primary completion date: Jun 2022 --> Jul 2024

Skin directed therapy includes steroids, nitrogen mustard, bexarotene gel, phototherapy UVB, and photochemiotherapy, i.e., total skin electron radiotherapy. Systemic therapies include retinoids, bexarotene, interferon, histone deacetylase inhibitors, photopheresis, targeted immunotherapy, and cytotoxic chemotherapy. Complexity of mycosis fungoides associated with long-term chronic evolution and multiple therapy based on disease stage need a multidisciplinary team approach to be treated.

P=N/A, N=32, Completed, Centre for Human Drug Research, Netherlands | Recruiting --> Completed

P2, N=100, Recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Trial completion date: Dec 2027 --> May 2028 | Trial primary completion date: Dec 2024 --> May 2025

The clinical profiles of hMF in Chinese population shared differences with other ethnic groups, but its histopathological, immunohistochemical results and prognosis condition were resembled with other previous reports. Hence, more patients were needed to find the characteristics of hMF.

P2, N=100, Recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Not yet recruiting --> Recruiting

P=N/A, N=30, Recruiting, Centre for Human Drug Research, Netherlands

P2, N=100, Not yet recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Trial completion date: Feb 2026 --> Nov 2027 | Trial primary completion date: Feb 2023 --> Nov 2024

The most common therapies prior to LCT were topical steroids (n=34), phototherapy (n=25), topical nitrogen mustard (n=20), oral retinoids (n=14), and oral methotrexate (n=8)...The most common treated for LCT was total skin electron beam therapy (TSEB, n=16) and chemotherapy (n=14), followed by brentuximab vedotin and localized RT in 9 patients each. Other treatments included topical corticosteroids (N=2), histone deacetylase inhibitors (n=4), and mogamulizumab (n=4)...Key pathologic and clinical variables such as CD30 percentage and t-cell gene rearrangement studies were not reported for many patients, suggesting standardized practices are needed in the diagnosis and pathologic evaluation of patients with tMF. Additional pathologic correlatives will be updated at the time of the presentation.

Our experience shows that acute viral infection and skin irritation appears at the beginning of the therapy. Topical mechlorethamine gel should be safe for longitudinal skin – directed therapy of MF, because only minor temporary cutaneous complications were observed.

Skin-directed therapies, such as phototherapy, radiation therapy, or topical nitrogen mustard, provide only short-term remissions...Many currently used therapies, such as interferon-α, imiquimod, extracorporeal phototherapy, and allogeneic bone marrow transplant, seem to exert their therapeutic effect via activation of the antitumor cytotoxic response and reconstitution of the host's immune system. It is likely that novel immunotherapies such as immune checkpoint inhibitors, cancer vaccines, and chimeric antigen receptor-T cells will help to manage CTCL more efficiently. We also discuss how current genomic techniques, such as estimating the mutational load by whole genome sequencing and neoantigen calling, are likely to provide clinically useful information facilitating personalized immunotherapy of CTCL.

Of the 15 patients who received cladribine in subsequent line, surgery (n=3), radiation (n=3), steroids (n=3), antibiotic with inhaled steroids (n=1), vinblastine (n=3), topical nitrogen mustard cream (n=1) and vemurafenib (n=1) were the treatments utilized before the initiation of cladribine. Responses were seen irrespective of the presence of BRAFV600E mutation. Cladribine was well tolerated overall, and may be considered a potential therapy for adult LCH patients.