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

This study has been terminated.
(The study was stopped due to low enrollment.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00127101
First received: August 2, 2005
Last updated: March 18, 2014
Last verified: March 2014
  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 1

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:


Further study details as provided by Merck Sharp & Dohme Corp.:

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
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 Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00127101     History of Changes
Other Study ID Numbers: 0683-016, MK0683-016, 2005_019
Study First Received: August 2, 2005
Results First Received: July 6, 2009
Last Updated: March 18, 2014
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 April 16, 2014