Clinical Trial: Therapeutic Efficacy of Topical Sirolimus in Early Stage Cutaneous T-cell Lymphoma (CTCL)

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: Therapeutic Efficacy of Topical Sirolimus in Early Stage Cutaneous T-cell Lymphoma (CTCL)

Brief Summary: The purpose of this study is to determine whether sirolimus reduces the symptoms of cutaneous T-cell lymphoma (CTCL) and whether it causes any side effects.

Detailed Summary:

This will be a prospective, non-randomized, open label study of topical sirolimus for the treatment of CTCL recurrent or refractory to at least one previous skin directed treatment. The purpose will be evaluation of safety and anti-tumor response as evaluated by serial skin examinations.

Study duration:

For subjects with at least partial remission, treatment will be continued for a maximum of 6 months. All subjects will be followed for 6 months from the time of discontinuation of the study drug or until progression of disease or until a new treatment for CTCL will be started.


Sponsor: Stefan Schieke MD

Current Primary Outcome: Overall Response Rate [ Time Frame: 6 months ]

Determine the efficacy of topical sirolimus in the treatment of early stage CTCL as overall response rate (ORR)

Response criteria:

Complete response (CR) will be defined as no evidence of clinical skin disease.

Partial response (PR) will be defined as a marked improvement in skin disease of > 50% from baseline without new lesions.

Stable disease (SD) will be defined as < 25% increase and < 50% clearance in skin disease from baseline without new lesions.

Progressive disease (PD) will be defined as > 25% increase in skin disease from baseline or new tumors or loss of response in those with CR or PR (increase in skin score of greater than the sum of nadir plus 50% baseline score).

The assessment will be based on Composite Assessment of Index Lesion Severity (CAILS) and, in case of more extensive disease, Modified Severity-Weighed Assessment Tool (mSWAT) scores.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Duration of objective response (DOR) [ Time Frame: 6 months ]
    Duration of objective response (DOR) - time from the first date of response until progression of disease or death due to the underlying lymphoma.
  • Adverse event profile and tolerability of topical sirolimus in patients with CTCL [ Time Frame: 6 months ]

    The safety and tolerability of the study treatment regimen will be evaluated. Analyses will be descriptive and no formal hypothesis testing will be performed.

    Safety endpoints will include treatment related adverse events. All reported adverse events will be graded using version 4.0 of the Common Terminology Criteria for Adverse Events (CTCAE v4.0).

    All adverse events recorded during the study will be summarized. The incidence of adverse events will be summarized by body system, severity (based on CTCAE grades), type of adverse event, and relation to the study drug. Deaths reportable as SAEs and non-fatal serious adverse events will be listed by patient and type of adverse event. Adverse events will be summarized by presenting the number and percentage of patients having any adverse event in each body system and having each individual adverse event.

  • Correlative biomarkers such as mTOR pathway activation at baseline and during treatment [ Time Frame: 6 months ]

    • Activation level of the mammalian target of rapamycin (mTOR) pathway, quantification of regulatory T cells (Tregs), cytokine profile in tissue samples. This part of the study will characterize the molecular events and mechanisms involved in the effect of sirolimus on CTCL. These studies will be performed in tissues samples from skin biopsies of patients upon study entry and during the study.

    1. mTOR pathway activity in skin:

      Assessment of phosphorylation status and expression level of downstream targets of mTOR with direct effects on cellular proliferation and growth. Those may include:

      • phospho-S6
      • phospho-4-EBP1
      • cyclin D1 levels

    2. Number of skin resident Tregs:

      Quantification of regulatory T cells characterized by surface marker expression pattern (CD4+, CD25+, FOXP3+) in tissue samples by immunohistochemistry and/or PCR/flow cytometry.

    3. Cytokine profile in skin:

    Characterization of cytokine profile in lesional skin will be done by cytokine PCR arrays.



Original Secondary Outcome: Same as current

Information By: Medical College of Wisconsin

Dates:
Date Received: April 24, 2013
Date Started: February 2014
Date Completion: December 2015
Last Updated: June 3, 2015
Last Verified: June 2015