Effect of Neurokinin-1 Receptor (NK1R) Antagonism on Pruritus in Patients With Sezary Syndrome

NCT01625455 | Terminated Phase 4 Results

• 1 other identifier: 110806
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this randomized, double-blinded, placebo-controlled study is to test the hypothesis that administration of aprepitant will decrease the severity of pruritus in patients with Sèzary Syndrome.

Conditions

Sezary Syndrome; Pruritus

Keywords

Sezary Syndrome; Pruritus; Aprepitant; Neurokinin-1

Outcome Measures

Primary Outcomes (1)

• Severity of Pruritus

  The primary endpoint is the severity of pruritus as measured on the visual analogue scale. A score of 100 indicated the worst pruritus imaginable, while 0 indicated no pruritus.

  one week

Secondary Outcomes (1)

• Quality of Life

  one week

Study Arms (2)

Aprepitant

ACTIVE COMPARATOR

Aprepitant will be given orally in a dose of 125mg on day 1 and 80mg daily on each subsequent day for a total of 7 days.

Drug: Aprepitant

Placebo

PLACEBO COMPARATOR

Matching placebo will be given in place of aprepitant

Drug: Placebo

Interventions

Aprepitant DRUG

Aprepitant will be given orally in a dose of 125mg on day 1 and 80mg daily on each subsequent day for a total of 7 days.

Also known as: Emend

Aprepitant

Placebo DRUG

Placebo will be given orally for a total of 7 days.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Known Sezary Syndrome
• Pruritus uncontrolled by conventional treatment. Baseline visual analogue scale \> 4.
• Age 18 through 80 years of age.
• Stable medication regimens for both Sezary Syndrome and pruritus for 3 months prior to study participation.

You may not qualify if:

• Known hepatic impairment (defined as liver function tests \>3 times the upper limit of normal).
• Pregnancy (all women of child-bearing potential will undergo urine beta-hcg testing).
• Concurrent use of pimozide, terfenadine, astemizole, or cisapride.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37235, United States

Location

Related Publications (13)

• Bernengo MG, Novelli M, Quaglino P, Lisa F, De Matteis A, Savoia P, Cappello N, Fierro MT. The relevance of the CD4+ CD26- subset in the identification of circulating Sezary cells. Br J Dermatol. 2001 Jan;144(1):125-35. doi: 10.1046/j.1365-2133.2001.04014.x.

  PMID: 11167693 BACKGROUND

• Booken N, Heck M, Nicolay JP, Klemke CD, Goerdt S, Utikal J. Oral aprepitant in the therapy of refractory pruritus in erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2011 Mar;164(3):665-7. doi: 10.1111/j.1365-2133.2010.10108.x. Epub 2011 Jan 28. No abstract available.

  PMID: 21039410 BACKGROUND

• Duval A, Dubertret L. Aprepitant as an antipruritic agent? N Engl J Med. 2009 Oct 1;361(14):1415-6. doi: 10.1056/NEJMc0906670. No abstract available.

  PMID: 19797294 BACKGROUND

• Cevikbas F, Steinhoff M, Ikoma A. Role of spinal neurotransmitter receptors in itch: new insights into therapies and drug development. CNS Neurosci Ther. 2011 Dec;17(6):742-9. doi: 10.1111/j.1755-5949.2010.00201.x. Epub 2010 Oct 15.

  PMID: 20950328 BACKGROUND

• Lambeir AM, Durinx C, Scharpe S, De Meester I. Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci. 2003 Jun;40(3):209-94. doi: 10.1080/713609354.

  PMID: 12892317 BACKGROUND

• Ahmad S, Wang L, Ward PE. Dipeptidyl(amino)peptidase IV and aminopeptidase M metabolize circulating substance P in vivo. J Pharmacol Exp Ther. 1992 Mar;260(3):1257-61.

  PMID: 1372050 BACKGROUND

• Heymann E, Mentlein R. Liver dipeptidyl aminopeptidase IV hydrolyzes substance P. FEBS Lett. 1978 Jul 15;91(2):360-4. doi: 10.1016/0014-5793(78)81210-1. No abstract available.

  PMID: 680144 BACKGROUND

• Mussap CJ, Geraghty DP, Burcher E. Tachykinin receptors: a radioligand binding perspective. J Neurochem. 1993 Jun;60(6):1987-2009. doi: 10.1111/j.1471-4159.1993.tb03484.x.

  PMID: 8388031 BACKGROUND

• Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008 Jun 5;358(23):2482-94. doi: 10.1056/NEJMra0706547. No abstract available.

  PMID: 18525044 BACKGROUND

• Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, Wood G, Dummer R, Ranki A, Burg G, Heald P, Pittelkow M, Bernengo MG, Sterry W, Laroche L, Trautinger F, Whittaker S; ISCL/EORTC. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007 Sep 15;110(6):1713-22. doi: 10.1182/blood-2007-03-055749. Epub 2007 May 31.

  PMID: 17540844 BACKGROUND

• Vonderheid EC, Bernengo MG, Burg G, Duvic M, Heald P, Laroche L, Olsen E, Pittelkow M, Russell-Jones R, Takigawa M, Willemze R; ISCL. Update on erythrodermic cutaneous T-cell lymphoma: report of the International Society for Cutaneous Lymphomas. J Am Acad Dermatol. 2002 Jan;46(1):95-106. doi: 10.1067/mjd.2002.118538.

  PMID: 11756953 BACKGROUND

• Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.

  PMID: 32632956 DERIVED

• Zic JA, Straka BT, McGirt LY, Nian H, Yu C, Brown NJ. Aprepitant for the Treatment of Pruritus in Sezary Syndrome: A Randomized Crossover Clinical Trial. JAMA Dermatol. 2018 Oct 1;154(10):1221-1222. doi: 10.1001/jamadermatol.2018.2510.

  PMID: 30140912 DERIVED

MeSH Terms

Conditions

Sezary Syndrome; Pruritus

Interventions

Aprepitant

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Nancy J. Brown, M.D., Principal Investigator
• Organization: VANDERBILT UNIVERSITY MEDICAL CENTER

nancy.j.brown@vanderbilt.edu

6153438701

Study Officials

• Nancy J Brown, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair and Physician-in-chief, Department of Medicine, Hugh Jackson Morgan Professor Medicine and Pharmacology, Vanderbilt University School of Medicine

Study Record Dates

• First Submitted: June 19, 2012
• First Posted: June 21, 2012
• Study Start: February 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2016
• Last Updated: May 10, 2017
• Results First Posted: May 10, 2017

Record last verified: 2017-03

Locations

US (1)