Cutaneous T-cell Lymphoma, Mycosis Fungoides, Sezary Syndrome
Conditions
Keywords
Cutaneous T-cell Lymphoma, CTCL, Mycosis Fungoides, Sezary Syndrome, Bexarotene, Targretin, Rosiglitazone, Avandia
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.
Interventions
DRUGRosiglitazone and Bexarotene
rosiglitazone added to bexarotene capsules
Sponsors
Vanderbilt University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a 50% Improvement in Baseline Skin Score | 16 weeks | mSWAT scoring. Range 0 to 400. Measured every 4 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life Evaluations | baseline and every 4 weeks | FACT-G, Functional Assessment of Cancer Therapy-General (quality-of-life scale) 0= worst 108=best |
| Pruritus Score | 16 weeks | 10-cm visual analog scale, 10= worst, 1=best |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Study All enrolled patients received rosiglitazone in addition to oral bexarotene | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Single Arm Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 53 years |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Number of Participants With a 50% Improvement in Baseline Skin Score
mSWAT scoring. Range 0 to 400. Measured every 4 weeks.
Time frame: 16 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rosiglitazone and Bexarotene | Number of Participants With a 50% Improvement in Baseline Skin Score | 0 participants |
Secondary
Pruritus Score
10-cm visual analog scale, 10= worst, 1=best
Time frame: 16 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rosiglitazone and Bexarotene | Pruritus Score | 5.7 units on a scale |
Secondary
Quality of Life Evaluations
FACT-G, Functional Assessment of Cancer Therapy-General (quality-of-life scale) 0= worst 108=best
Time frame: baseline and every 4 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rosiglitazone and Bexarotene | Quality of Life Evaluations | 86.25 units on a scale |