An Investigational Study of a Histone Deacetylase (HDAC) Inhibitor Plus Targretin in Cutaneous T-Cell Lymphoma Patients (0683-016)(TERMINATED)

Study Overview
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Brief Summary
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This is an investigational study that increases the dosage to determine the safety/tolerability, and efficacy of a histone deacetylase inhibitor in combination with Targretin in patients with cutaneous T-cell lymphoma in patients who have failed at least one prior systemic therapy.

Official Title
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A Phase I Clinical Trial of Oral Suberoylanilide Hydroxamic Acid (Vorinostat; Zolinza) in Combination With Bexarotene in Patients With Advanced Cutaneous T-Cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: vorinostat
* Drug: Comparator: bexarotene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men greater than or equal to 18 years of age Advanced cutaneous T-cell lymphoma, stage IB or higher including Sezary Syndrome with progressive, persistent, or recurrent disease Failure of at least one systemic therapy, not including Bexarotene (Targretin) Eastern Cooperative Oncology Group (ECOG) status less than or equal to 2 (measurement to determine your ability to perform daily activities) Exclusion Criteria: Patient has had investigational treatment in the preceding 30 days Active hepatitis B or C, history of HIV Prior treatment with any HDAC inhibitor Patients must be disease free from prior malignancies for greater than 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Vorinostat 200 milligrams daily for 7 days per week + Bexarotene 150 milligrams/meter[2] daily x 7 days per week | Drug: vorinostat<br>* Dose escalation study starting with vorinostat 200 mg q.d. capsules (1 capsule daily) and rising up to vorinostat 400 mg q.d. capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Zolinza;Drug: Comparator: bexarotene<br>* Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Targretin;|
| Experimental: Cohort 2<br>Vorinostat 300 milligrams daily for 7 days per week + Bexarotene 150 milligrams/meter[2] daily x 7 days per week | Drug: vorinostat<br>* Dose escalation study starting with vorinostat 200 mg q.d. capsules (1 capsule daily) and rising up to vorinostat 400 mg q.d. capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Zolinza;Drug: Comparator: bexarotene<br>* Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Targretin;|
| Experimental: Cohort 2a<br>Vorinostat 200 milligrams daily for 7 days per week + Bexarotene 225 milligrams/meter[2] daily x 7 days per week | Drug: vorinostat<br>* Dose escalation study starting with vorinostat 200 mg q.d. capsules (1 capsule daily) and rising up to vorinostat 400 mg q.d. capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Zolinza;Drug: Comparator: bexarotene<br>* Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Targretin;|
| Experimental: Cohort 2b<br>Vorinostat 200 milligrams daily for 7 days per week + Bexarotene 300 milligrams/meter[2] daily x 7 days per week | Drug: vorinostat<br>* Dose escalation study starting with vorinostat 200 mg q.d. capsules (1 capsule daily) and rising up to vorinostat 400 mg q.d. capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Zolinza;Drug: Comparator: bexarotene<br>* Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Targretin;|
| Experimental: Cohort 6<br>Vorinostat 400 milligrams daily for 7 days per week + Bexarotene 150 milligrams daily for 7 days per week | Drug: vorinostat<br>* Dose escalation study starting with vorinostat 200 mg q.d. capsules (1 capsule daily) and rising up to vorinostat 400 mg q.d. capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Zolinza;Drug: Comparator: bexarotene<br>* Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Targretin;|
| Experimental: Cohort 7<br>Vorinostat 400 milligrams daily for 7 days per week + Bexarotene daily for 7 days per week [150 milligrams (Cycle 1) 225 milligrams (Cycle 2-6) | Drug: vorinostat<br>* Dose escalation study starting with vorinostat 200 mg q.d. capsules (1 capsule daily) and rising up to vorinostat 400 mg q.d. capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Zolinza;Drug: Comparator: bexarotene<br>* Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment.<br>* Other names: Targretin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | Number of patients with Dose Limiting Toxicities (DLT). A DLT is an adverse event that determined the treatment dose level was not tolerable for that patient in Cycle 1. | Day 1 to day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Responded to Treatment | Disease burden as assessed by the pre-specified Severity Weighted Assessment Tool (SWAT) measurement. A Response is defined as equal to or greater than 50% improvement in SWAT score. SWAT Score is determined by the Lesions classified as patch, plaque, or tumor. The sum of percent of total body surface area (%TBSA) by lesion type is derived and multiplied by a factor of 1 (for patch), 2 (for plaque), or 4 (for tumor). The skin score total is derived by summing the skin score subtotals for patches, plaques and tumors. The skin score total is dimensionless and can range from 0 to 400 | Every 28 days for up to 6 Months of Treatment |