An Investigational Study of a Histone Deacetylase (HDAC) Inhibitor Plus Targretin in Cutaneous T-Cell Lymphoma Patients - Full Text View

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00127101

Purpose

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.

Condition	Intervention	Phase
Lymphoma	Drug: vorinostat Drug: Comparator: bexarotene	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Clinical Trial of Oral Suberoylanilide Hydroxamic Acid (Vorinostat; Zolinza) in Combination With Bexarotene in Patients With Advanced Cutaneous T-Cell Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Suberoylanilide hydroxamic acid Bexarotene

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities [ Time Frame: Day 1 to day 28 ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

Number of Participants Who Responded to Treatment [ Time Frame: Every 28 days for up to 6 Months of Treatment ] [ Designated as safety issue: No ]
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

Enrollment:	23
Study Start Date:	September 2005
Study Completion Date:	October 2008
Estimated Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1 Vorinostat 200 milligrams daily for 7 days per week + Bexarotene 150 milligrams/meter[2] daily x 7 days per week	Drug: vorinostat 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. Other Name: Zolinza Drug: Comparator: bexarotene Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment. Other Name: Targretin
Experimental: Cohort 2 Vorinostat 300 milligrams daily for 7 days per week + Bexarotene 150 milligrams/meter[2] daily x 7 days per week	Drug: vorinostat 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. Other Name: Zolinza Drug: Comparator: bexarotene Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment. Other Name: Targretin
Experimental: Cohort 2a Vorinostat 200 milligrams daily for 7 days per week + Bexarotene 225 milligrams/meter[2] daily x 7 days per week	Drug: vorinostat 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. Other Name: Zolinza Drug: Comparator: bexarotene Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment. Other Name: Targretin
Experimental: Cohort 2b Vorinostat 200 milligrams daily for 7 days per week + Bexarotene 300 milligrams/meter[2] daily x 7 days per week	Drug: vorinostat 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. Other Name: Zolinza Drug: Comparator: bexarotene Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment. Other Name: Targretin
Experimental: Cohort 6 Vorinostat 400 milligrams daily for 7 days per week + Bexarotene 150 milligrams daily for 7 days per week	Drug: vorinostat 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. Other Name: Zolinza Drug: Comparator: bexarotene Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment. Other Name: Targretin
Experimental: Cohort 7 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 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. Other Name: Zolinza Drug: Comparator: bexarotene Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment. Other Name: Targretin

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00127101

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

No publications provided

Responsible Party:	Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00127101 History of Changes
Other Study ID Numbers:	2005_019, MK0683-016
Study First Received:	August 2, 2005
Results First Received:	July 6, 2009
Last Updated:	April 7, 2010
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bexarotene

Vorinostat
Histone Deacetylase Inhibitors
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012