The purpose of this trial is to determine if combination therapy with rosiglitazone and bexarotene might have a synergistic effect in the treatment of patients with CTCL...
Date First Received: September 12, 2005
Last Updated: October 17, 2007
Verified by: Vanderbilt University, October 2007
Clinical Trial Phase: Phase 2 | Start Date: June 2005
Overall Status: Completed
Estimated Enrollment: 10
Brief Summary
Official Title: “Open Label Pilot Study of Combination Therapy With Rosiglitazone and Bexarotene to Investigate a Possible Synergism in the Treatment of Cutaneous T-Cell Lymphoma”
Condition Keyword(s):
Intervention(s):
The purpose of this trial is to determine if combination therapy with rosiglitazone and bexarotene might have a synergistic effect in the treatment of patients with CTCL.
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Detailed Clinical Trial Description
Treatment options for CTCL include both skin-directed and systemic therapies. Topical treatments are effective for early-stage disease that is localized to the skin. However, disease involving the lymph nodes or visceral sites can be palliated but rarely cured, even with the most aggressive regimens of systemic chemotherapy. Unfortunately, current treatment options at this stage only provide a short term response. Thus, it is important that additional therapies are investigated to manage this malignancy.
Bexarotene has been approved by the FDA for the treatment of Cutaneous T-Cell Lymphoma (CTCL).Bexarotene binds the RXR(Retinoid X Receptor)inside the cell, a receptor that forms heterodimers with a multitude of other nuclear receptors. One of these is the PPARĪ³ (Peroxisome Proliferator Activator Receptor Gamma), a nuclear receptor that binds Rosiglitazone.Rosiglitazone is an FDA approved antidiabetic agent of the Thiazolidinedione class. Rosiglitazone increases insulin sensitivity and is useful in the treatment of type 2 diabetes. In vitro data suggest that rosiglitazone and bexarotene may act synergistically to induce apoptosis in cell lines derived from patients with cutaneous T cell lymphoma (CTCL).
This pilot study will investigate this possible synergism in a small cohort of patients with stable or progressive CTCL already being treated with bexarotene.
Intervention(s) in this Clinical Trial
- Drug: Rosiglitazone
Outcome Measures for this Clinical Trial
Primary Measures
- Skin score calculated monthly at clinic visits.
Secondary Measures
- The safety and tolerability of combination therapy with bexarotene and rosiglitazone assessed every two weeks via laboratory testing and every four weeks via quality of life evaluations.
Criteria for Participation in this Clinical Trial
Inclusion Criteria:
- Patients with biopsy proven persistent or recurrent cutaneous cell lymphoma (CTCL) Stage IA-IVA
- Patients with a pathologic proven diagnosis of CTCL that is documented in the patient history.
- Patient has preserved organ function.
- Patient has an ECOG performance status between 0 - 2.
- Women of childbearing potential should be screened for pregnancy prior to treatment and utilize effective contraceptive methods (e.g. barrier) during treatment period.
- Patients over the age of 18 who are willing and able to provide Informed Consent
- The patient has been taking Targretin capsules for at least the last 4 months and the dose has remained relatively stable.
- The patient has had stable or progressive disease over the past 4 months.
- Patient has adequate laboratory parameters for liver and kidney function.
Exclusion Criteria:
- Patients with CD30+ Anaplastic Large Cell Lymphoma
- Patients with pathology consistent with peripheral T-cell lymphoma.
- Patients with Stage IVB (visceral involvement with CTCL).
- Patients with history of Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis
- C infection.
- Patients with a diagnosis of congestive heart failure.
- Patients exhibiting significant edema or unstable cardiovascular disease.
- Patients with a fasting triglyceride level greater then 500mg/dl.
- Patients that have started any new treatment for CTCL in the past 4 months.
- Pregnant women will be excluded from the study.
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Sponsor Information
Lead Sponsor: Vanderbilt University
Overall Clinical Trial Officials and Contacts
John A Zic, MD Principal Investigator Vanderbilt University
Related Publications
References
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Koh HK, Charif M, Weinstock MA. Epidemiology and clinical manifestations of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 1995 Oct;9(5):943-60. Review.
Duvic M, Hymes K, Heald P, Breneman D, Martin AG, Myskowski P, Crowley C, Yocum RC; Bexarotene Worldwide Study Group. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol. 2001 May 1;19(9):2456-71.
Zhang C, Ni X, Konopleva M, Andreeff M, Duvic M. The novel synthetic oleanane triterpenoid CDDO (2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid) induces apoptosis in Mycosis fungoides/Sezary syndrome cells. J Invest Dermatol. 2004 Aug;123(2):380-7.
Carr A, Workman C, Carey D, Rogers G, Martin A, Baker D, Wand H, Law M, Samaras K, Emery S, Cooper DA; Rosey investigators. No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial. Lancet. 2004 Feb 7;363(9407):429-38.
Wang TD, Chen WJ, Lin JW, Chen MF, Lee YT. Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome. Am J Cardiol. 2004 Feb 1;93(3):362-5.
Raji A, Seely EW, Bekins SA, Williams GH, Simonson DC. Rosiglitazone improves insulin sensitivity and lowers blood pressure in hypertensive patients. Diabetes Care. 2003 Jan;26(1):172-8.
Demierre MF, Tien A, Miller D. Health-related quality-of-life assessment in patients with cutaneous T-cell lymphoma. Arch Dermatol. 2005 Mar;141(3):325-30.
Bunn PA Jr, Lamberg SI. Report of the Committee on Staging and Classification of Cutaneous T-Cell Lymphomas. Cancer Treat Rep. 1979 Apr;63(4):725-8. No abstract available.
Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S, Diaz-Perez JL, Geerts ML, Goos M, Knobler R, Ralfkiaer E, Santucci M, Smith N, Wechsler J, van Vloten WA, Meijer CJ. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood. 1997 Jul 1;90(1):354-71. Review.
Shapiro PE. Advances in the histologic diagnosis of cutaneous T-cell lymphoma. Adv Dermatol. 1996;11:255-84; discussion 285. Review. No abstract available.
Additional Information
Information obtained from ClinicalTrials.gov on September 05, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00178841
Study ID Number: 050416
ClinicalTrials.gov Identifier: NCT00178841
Health Authority: United States: Food and Drug Administration
Clinical Trials Authorship and Review
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