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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: vorinostat

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vorinostat	Drug: vorinostat; Parts I & II: Vorinostat (400 mg) Oral, daily (QD). Treatment period is 28 days per cycle.; Other Names: Zolinza; MK-0683

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Wada H, Tsuboi R, Kato Y, Sugaya M, Tobinai K, Hamada T, Shimamoto T, Noguchi K, Iwatsuki K. Phase I and pharmacokinetic study of the oral histone deacetylase inhibitor vorinostat in Japanese patients with relapsed or refractory cutaneous T-cell lymphoma. J Dermatol. 2012 Oct;39(10):823-8. doi: 10.1111/j.1346-8138.2012.01554.x. Epub 2012 Apr 16.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: October 9, 2008
• First Submitted That Met QC Criteria: October 9, 2008
• First Posted (Estimate): October 13, 2008

Study Record Updates

• Last Update Posted (Estimate): April 21, 2015
• Last Update Submitted That Met QC Criteria: April 2, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Vorinostat
• Other Study ID Numbers: 0683-089; 2008_565