Vorinostat (MK-0683) Phase I Study in Cutaneous T-Cell Lymphoma (CTCL) Patients (MK-0683-089 EXT1)

Study Overview
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Brief Summary
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Part I evaluates the safety, tolerability and pharmacokinetics (PK) of vorinostat in Japanese patients with relapsed or refractory CTCL. Part II evaluates the safety of vorinostat in Japanese pts. with relapsed or refractory CTCL. Relapsed or refractory CTCL patients will be newly enrolled in Part II.

Official Title
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Phase I Clinical Study of MK-0683 in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma (CTCL)

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: vorinostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Parts I & II): Patients With CTCL Who Have Progressive, Persistent Or Recurrent Disease Subsequent To At Least One Prior Therapy Eastern Cooperative Oncology Group (ECOG) Performance Status Must Be 0-2 Patients Have Adequate Bone Marrow, Liver Function And Renal Function Exclusion Criteria (Parts I & II): Patients Had Prior Therapy Within 3 Weeks Before Registration, Or Have Not Recovered From Toxicities Of Prior Therapy Patients Have Uncontrolled Intercurrent Illness Pregnant Or Women Have A Will To Be Pregnant And Lactating Woman

Ages Eligible for Study
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Minimum Age: 20 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: Vorinostat<br> | Drug: vorinostat<br>* Parts I & II: Vorinostat (400 mg) Oral, daily (QD). Treatment period is 28 days per cycle.<br>* Other names: Zolinza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts I & II: Number of Participants Experiencing Clinical or Laboratory Adverse Experiences (AE) | A laboratory AE is defined as any unfavorable & unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A clinical AE is defined similarly but also includes changes in structure or function of the body. | Day 1 up until 30 days post study completion or early termination (up to approximately 506 days) | 
| Part I: Number of Participants Experiencing Dose Limiting Toxicity (DLT) | A DLT was defined as any of the following (per Common Terminology Criteria for Adverse Events [CTCAE] version 3.0): Grade 3 (severe)-4 (life-threatening) neutropenia with fever ≥ 38.5ºC Grade 3-4 neutropenia with an infection requiring antibiotic or antifungal treatment Grade 4 neutropenia lasting at least 5 days Grade 4 thrombocytopenia Other Grade 4 hematologic toxicity, including a decrease in hemoglobin, only at the discretion of the principal investigator Grade 3 or 4 non-hematologic event, except which are manageable by supportive care or non-prohibited therapies | Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part I: Total Drug Exposure (Area Under the Concentration Curve, AUC[0-24 Hours]) | Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat. | Days 1 & 28 of Cycle 1 | 
| Part I: Maximum Drug Concentration (Cmax) | Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat. | Days 1 & 28 of Cycle 1 | 
| Part I: Time at Which Cmax Occurs (Tmax) | Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat. | Days 1 & 28 of Cycle 1 | 
| Part I: The Amount of Time it Takes for the Drug Concentration to Decrease by Half (T1/2) | Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat. | Days 1 & 28 of Cycle 1 |