Clinical trial NCT00178841: Combination Drug Study of Bexarotene and Rosiglitazone to Treat CTCL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cutaneous T-cell Lymphoma
Mycosis Fungoides
Sezary Syndrome
Keywords: Cutaneous T-cell Lymphoma
CTCL
Mycosis Fungoides
Sezary Syndrome
Bexarotene
Targretin
Rosiglitazone
Avandia
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
First posted: 2005-09-15
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 PPARγ (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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With a 50% Improvement in Baseline Skin Score
timeFrame: 16 weeks
Secondary outcomes:
measure: Quality of Life Evaluations
timeFrame: baseline and every 4 weeks
measure: Pruritus Score
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: John A Zic, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bunn PA Jr, Hoffman SJ, Norris D, Golitz LE, Aeling JL. Systemic therapy of cutaneous T-cell lymphomas (mycosis fungoides and the Sezary syndrome). Ann Intern Med. 1994 Oct 15;121(8):592-602. doi: 10.7326/0003-4819-121-8-199410150-00007.
citation: 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.
citation: 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. doi: 10.1200/JCO.2001.19.9.2456.
citation: 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. doi: 10.1111/j.0022-202X.2004.23207.x.
citation: 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. doi: 10.1016/S0140-6736(04)15489-5.
citation: 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. doi: 10.1016/j.amjcard.2003.10.022.
citation: 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. doi: 10.2337/diacare.26.1.172.
citation: 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. doi: 10.1001/archderm.141.3.325.
citation: 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.
citation: 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.
citation: Shapiro PE. Advances in the histologic diagnosis of cutaneous T-cell lymphoma. Adv Dermatol. 1996;11:255-84; discussion 285. No abstract available.