Combination Drug Study of Bexarotene and Rosiglitazone to Treat CTCL

Study Overview
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Brief Summary
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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
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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.

Official Title
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Open Label Pilot Study of Combination Therapy With Rosiglitazone and Bexarotene to Investigate a Possible Synergism in the Treatment of Cutaneous T-Cell Lymphoma

Conditions
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Sezary Syndrome, Cutaneous T-cell Lymphoma, Mycosis Fungoides

Intervention / Treatment
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* Drug: Rosiglitazone and Bexarotene


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Rosiglitazone and Bexarotene|rosiglitazone added to bexarotene capsules|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a 50% Improvement in Baseline Skin Score | mSWAT scoring. Range 0 to 400. Measured every 4 weeks. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Evaluations | FACT-G, Functional Assessment of Cancer Therapy-General (quality-of-life scale) 0= worst 108=best | baseline and every 4 weeks | 
| Pruritus Score | 10-cm visual analog scale, 10= worst, 1=best | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cutaneous T-cell Lymphoma, CTCL, Mycosis Fungoides, Sezary Syndrome, Bexarotene, Targretin, Rosiglitazone, Avandia