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

Abstract

Objective: To evaluate the efficacy and safety of a novel mechlorethamine hydrochloride, 0.02%, gel in mycosis fungoides. DESIGN Randomized, controlled, observer-blinded, multicenter trial comparing mechlorethamine, 0.02%, gel with mechlorethamine, 0.02%, compounded ointment. Mechlorethamine was applied once daily for up to 12 months. Tumor response and adverse events were assessed every month between months 1 and 6 and every 2 months between months 7 and 12. Serum drug levels were evaluated in a subset of patients.

Setting: Academic medical or cancer centers.

Patients: In total, 260 patients with stage IA to IIA mycosis fungoides who had not used topical mechlorethamine within 2 years and were naive to prior use of topical carmustine therapy.

Main outcome measures: Response rates of all the patients based on a primary clinical end point (Composite Assessment of Index Lesion Severity) and secondary clinical end points (Modified Severity-Weighted Assessment Tool and time-to-response analyses).

Results: Response rates for mechlorethamine gel vs ointment were 58.5% vs 47.7% by the Composite Assessment of Index Lesion Severity and 46.9% vs 46.2% by the Modified Severity-Weighted Assessment Tool. By the Composite Assessment of Index Lesion Severity, the ratio of gel response rate to ointment response rate was 1.23 (95% CI, 0.97-1.55), which met the prespecified criterion for noninferiority. Time-to-response analyses demonstrated superiority of mechlorethamine gel to ointment (P< .01). No drug-related serious adverse events were seen. Approximately 20.3% of enrolled patients in the gel treatment arm and 17.3% of enrolled patients in the ointment treatment arm withdrew because of drug-related skin irritation. No systemic absorption of the study medication was detected.

Conclusion: The use of a novel mechlorethamine, 0.02%, gel in the treatment of patients with mycosis fungoides is effective and safe.

Trial registration: clinicaltrials.gov Identifier:NCT00168064.

Figure 1

Flow diagram of subject progress through the randomized trial.

Figure 2

Ratios of response rates for primary (CAILS) and secondary (mSWAT) efficacy endpoints in ITT and EE populations with 95% confidence intervals greater than non-inferiority threshold (0.75).

Figure 3

Kaplan-Meier curve of time to response by CAILS response in ITT population: 50% RR in the MCH gel arm was at 26 weeks and at 42 weeks in the MCH ointment arm.

Figure 4

Kaplan-Meier curve of duration of response (DOR) by CAILS score in ITT population: at least 90% of responses will be maintained for 10+ months with no statistical significant difference between the two treatment arms (p=0.481 log-rank).