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

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.

Study Overview

• Status: Withdrawn
• Conditions: Cutaneous T-cell Lymphoma (CTCL)
• Intervention / Treatment: Drug: Sirolimus 0.1% Ointment

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinically and histologically confirmed diagnosis of CTCL (early stage disease with patches and/or thin plaques covering up to 10%, stage IA)
• Relapsed or refractory disease after at least one standard skin directed treatment including corticosteroids, topical bexarotene, phototherapy
• All subjects must be 18 years of age or older
• Life expectancy ≥ 6 months, determined by the treating physician
• Signed informed consent

Exclusion Criteria:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including topical or systemic glucocorticosteroids, chemotherapy, radiation therapy, antibody based therapy, etc.)
• Prior treatment with any investigational drug within the preceding 4 weeks
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent.
• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Adequate contraception (oral contraceptives ("the pill"), intrauterine devices (IUDs), contraceptive implants under the skin, or contraceptive injections, diaphragms with spermicide and condoms with foam) must be used throughout the trial and for 8 weeks after the last dose of study drug (women of childbearing potential must have a negative urine within 7 days prior to administration of sirolimus).
• Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus).
• Patients with a known hypersensitivity to sirolimus or other rapamycin (e.g., everolimus, temsirolimus) or to its excipient
• History of noncompliance to medical regimens
• Patients unwilling to or unable to comply with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sirolimus 0.1% ointment	Drug: Sirolimus 0.1% Ointment; Sirolimus 0.1% ointment will be applied topically to all affected areas of the skin twice daily for 6 months or until progression or unacceptable toxicity.; Other Names: Rapamune, sirolimus, rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of objective response (DOR)	Duration of objective response (DOR) - time from the first date of response until progression of disease or death due to the underlying lymphoma.	6 months
Adverse event profile and tolerability of topical sirolimus in patients with CTCL	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.	6 months
Correlative biomarkers such as mTOR pathway activation at baseline and during treatment	• 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.; 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-S6phospho-4-EBP1cyclin D1 levels; 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.; Cytokine profile in skin: Characterization of cytokine profile in lesional skin will be done by cytokine PCR arrays.	6 months

Collaborators and Investigators

• Sponsor: Stefan Schieke MD
• Investigators: Principal Investigator: Stefan Schieke, MD, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): May 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: April 24, 2013
• First Submitted That Met QC Criteria: April 30, 2013
• First Posted (Estimate): May 1, 2013

Study Record Updates

• Last Update Posted (Estimate): June 4, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: CTCL; Early stage; Cutaneous T-cell Lymphoma; Stage 1A
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: PRO#00019812