Impact of Vorinostat on Pruritus Signaling Pathways - Merck Study
Mycosis Fungoides (MF) is a rare malignancy in the United States. It is the most common form of cutaneous T-cell lymphoma (CTCL). Sézary syndrome (SS) is the most severe and leukemic form of CTCL. Pruritus, or itch, is defined as an unpleasant sensation that elicits the desire to scratch. Severe itch is a manifestation of all forms of MF, especially those with patch/plaque and folliculotropic variants, as well as in Sezary patients. While severe itch causes great suffering for patients, the pathogenesis of itch in MF and Sezary syndrome is complex and not well understood. It is thought that various chemical mediators are produced by the malignant cells to cause itch. Vorinostat, an FDA approved therapy for the treatment of MF, has also been reported to relieve pruritis. The goal of the study is to evaluate how vorinostat affects different chemicals in the skin that have been known to cause itch. This is a single center, non-randomized study designed to obtain and test blood and skin tissue samples take at various time-points over 6 months in patients who are prescribed vorinostat per standard of care treatment. Samples from pruritic and non-pruritic skin and blood of MF and Sezary patients will be evaluated for the presence of chemicals thought to be important in the cause of itch in these diseases. This evaluation will include immunohistochemistry, RT-PCR, and ELISA assays. The results from this study may help define how vorinostat decreases itch in patients with MF and Sezary Syndrome.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||A Phase IV Study Of The Impact Of Vorinostat On Cellular Signaling And Cytokine Production In Cutaneous T-Cell Lymphoma Patients With Pruritus|
- the percentage change in pSTAT3 expression among patients reporting a relief in their pruritus, irrespective of lesion clearing [ Time Frame: 6 months ] [ Designated as safety issue: No ]
For each time point and each skin type, pSTAT3 staining will be measured as strong (2+), weak (1+), none (0). At each time point, patients will report pruritus on a visual analogue score (VAS) from 0-100 mm (0, none; 100, worst imaginable). Meaningful change in pruritus is a change in VAS score of 30 mm or more from baseline to the third time point (a change measure that will also be computed for all endpoints; the baseline to time 3 measure being of primary clinical interest).
Spearman rank correlation will examine the significance of the association between the change in cytoplasmic staining intensity and change in pruritus as assessed by subjects with the visual analog scale, neither of which will be assumed to follow a Gaussian distribution.
For descriptive purposes only, analyses will also be performed stratified on pruritis stage at baseline (early stage I-IIA vs. late stage IIB-IVB and pruritus, mild VAS less than 40 vs. moderate to severe VAS greater than 40, up to 100).
- IL-31 amount and intensity of cathepsin S expression [ Time Frame: 6 months ] [ Designated as safety issue: No ]
IL31 amount and cathepsin S intensity of expression will be determined at 3 time points described above and also from itchy and non-itchy skin at each time point. The goal is to determine if there is an association between a change (presumably a decrease) in these targets and an improvement in pruritus as reported by the VAS score.
Spearman rank correlation will examine the significance of the association between the change in amount of IL-31 or level of cathepsin S expression and change in pruritus as assessed by subjects with the visual analog scale, neither of which will be assumed to follow a Gaussian distribution.
For this data, taken in separate locations (treatment, control) on the same individuals, we will perform paired t-tests or non-parametric Wilcoxon signed rank tests as appropriate.
- percentage of vasodilatory peptidergic nerves at the dermoepidermal junction as a percentage of total nerves [ Time Frame: 6 months ] [ Designated as safety issue: No ]
The total nerve length of all nerves and the total nerve length of nerves expressing vasodilatory peptidergic markers will be determined in the skin biopsies at 3 time points described above, and the percentage calculated.
Spearman rank correlation will examine the significance of the association between the change in the above percentage of nerves and change in pruritus as assessed by subjects with the visual analog scale, neither of which will be assumed to follow a Gaussian distribution.
For this data taken in separate locations (treatment, control) on the same individuals, we will perform paired t-tests or non-parametric Wilcoxon signed rank tests as appropriate.
Biospecimen Retention: Samples With DNA
Blood Samples Skin biopsies
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
MF patients for blood & biopsy
Participants who are cared for at Boston Medical Center will first be assessed by physicians of the CTCL multi-specialty clinic if vorinostat, administered per standard of care, is an appropriate therapy for their CTCL. The decision to invite patients to participate in this study is (1) separate from the above described clinical decision to utilize vorinostat, and (2) will be offered subsequent to the clinical decision to utilize vorinostat. Vorinostat (Zolinza) will be administered as follows: each subject will receive each month for the first 3 months (cycle 1 to 3) 3 capsules of vorinostat 100 mg po daily. For months 4-6 (cycles 4 to 6), subjects will receive each month for 4 capsules of vorinostat 100 mg po daily.
Two 6 mm skin punch biopsies (one from pruritic skin and from involved non pruritic skin).Procedure: Blood
Peripheral blood (10 mls) to be drawn and used for cytokine analysis.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01801670
|Contact: Deon Wolpowitz, MD, PhDfirstname.lastname@example.org|
|United States, Massachusetts|
|Boston University||Not yet recruiting|
|Boston, Massachusetts, United States, 02118|
|Contact: Deon Wolpowitz, MD, PhD 617-638-5542 email@example.com|
|Principal Investigator:||Deon Wolpowitz, MD, PhD||Boston University|