Phase I Study of Topical Romidepsin (Depsipeptide) in Early Stage Cutaneous T-Cell Lymphoma
- Romidepsin is a histone deacetylase inhibitor which has demonstrated efficacy and
tolerability as an infusion in later stages of cutaneous T-cell lymphoma (CTCL).
- Early stages of CTCL are typically treated with skin-directed therapies, which may lose
efficacy over time and have adverse effects (i.e. risk of secondary skin cancers,
difficulty of use).
- A topical form of romidepsin may be helpful in the treatment of early-stage CTCL.
- Primary - To define the maximal tolerated dose (MTD) of topical romidepsin for
early-stage CTCL when administered three times weekly, then escalated first in
concentration, followed by increased frequency and lastly over increasing body surface
- Secondary - To assess histone acetylation in topical romidepsin-treated skin.
- Secondary - To assess in a pilot fashion clinical efficacy of topical romidepsin in
early stage cutaneous T-cell lymphoma.
- Secondary - To perform pharmacokinetic monitoring of blood levels of romidepsin in
topically treated patients.
-Patients age greater than or equal to 18 with confirmed early-stage (stage IA, IB, or IIA)
cutaneous T-cell lymphoma.
- A Cohorts of Three design to define the MTD of topical romidepsin in
Aquaphor(Registered Trademark) ointment initially applied overnight, three times weekly
for 4 weeks, then escalated first in concentration, followed by increased frequency and
lastly over increasing body surface areas.
- Skin toxicities, systemic toxicities, and disease response will be assessed throughout
- The primary focus of the first part of the protocol will be to evaluate local skin
toxicity, beginning with dose level 1 of 0.05 percent topical romidepsin on 25 cm(2)
target area (0.005 mg/ cm(2). If tolerated, progress to higher dose levels of 0.25
percent (0.025 mg/ cm(2); dose level 2) and then 0.5 percent (0.05 mg/ cm(2); dose
level 3) topical romidepsin on 25 cm(2) target area. Systemic toxicity will also be
- To date, we have completed the first 4 dose levels and have not yet established
cutaneous MTD. To achieve this, we will proceed to the second part of the protocol,
which will increase the concentration to 1%, then increase the frequency to daily
application, then progress to 2% concentration, then 4% concentration, and then
applying to progressively larger body surface areas. Our aim is to more fully address
systemic toxicity by increasing drug concentration, application frequency, and body
surface area (BSA) treated. We will utilize topical romidepsin at the MTD on increasing
BSA (lesional & nonlesional skin): multiple lesions up to 3% BSA (dose level 4),
multiple lesions up to 25% BSA (dose level 7A), 50% BSA (dose level 7B), and 75% or >
BSA (dose level 7C).
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To define the maximal tolerated dose of topical romidepsin.
Deborah E Citrin, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|