Vorinostat in Patients With Primary Cutaneous T-Cell Lymphoma

This study is currently recruiting participants.
Verified September 2013 by University of Washington
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT00958074
First received: August 10, 2009
Last updated: September 20, 2013
Last verified: September 2013
  Purpose

This phase II trial studies the side effects and how well vorinostat works in treating patients with primary cutaneous T-cell lymphoma. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth


Condition Intervention Phase
Stage I Cutaneous T-cell Non-Hodgkin Lymphoma
Stage I Mycosis Fungoides/Sezary Syndrome
Stage II Cutaneous T-cell Non-Hodgkin Lymphoma
Stage II Mycosis Fungoides/Sezary Syndrome
Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
Stage III Mycosis Fungoides/Sezary Syndrome
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IV Mycosis Fungoides/Sezary Syndrome
Drug: vorinostat
Other: flow cytometry
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Prospective Non-Randomized Two-Arm Clinical Trial of Dose-Adjusted Schedule of Vorinostat in Patients With Primary Cutaneous T-Cell Lymphoma (CTCL) Who Did Not Receive Prior Systemic Therapy or Have Been Treated With Single Agent Targretin

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Objective response [ Time Frame: After at least 28 days ] [ Designated as safety issue: No ]
    Defined as either no evidence of clinical disease or marked improvement (>= 50%) decrease in the modified Severity-Weighted Assessment Tool (mSWAT) skin assessment score compared to baseline.


Secondary Outcome Measures:
  • Objective response rate of extracutaneous manifestations of CTCL (lymph node enlargement, Sezary cells in peripheral blood); [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: No ]
    Assessed by changes in the sum of the products in the greatest diameters of enlarged lymph nodes by serial computed tomography (CT) or positron emission tomography (PET)/CT scans.

  • Safety and tolerability of dose-adjusted vorinostat [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
    Toxicities will be graded in severity according to the guidelines outlined in the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.

  • Changes in sezary cell count measured by serial flow cytometry measurements [ Time Frame: Baseline to 30 days post-treatment ] [ Designated as safety issue: No ]
  • Changes in the Physicians serial assessment of erythroderma score [ Time Frame: Baseline to 30 days post-treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: July 2009
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort I (greater than or equal to 65 years old)
Patients receive 200 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Other: flow cytometry
correlative study
Other: laboratory biomarker analysis
correlative study
Experimental: Cohort II (less than 65 years old)
Patients receive 400 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Other: flow cytometry
correlative study
Other: laboratory biomarker analysis
correlative study

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the objective response rate to treatment with dose-adjusted Vorinostat schedule in subjects with cutaneous T-cell lymphoma (CTCL) who did not receive prior systematic therapy or have been treated with single agent targretin (bexarotene).

SECONDARY OBJECTIVES:

I. To determine the safety and tolerability of dose-adjusted Vorinostat schedule when administered to patients with primary cutaneous T-cell lymphoma who did not receive prior systematic therapy or have been treated with single agent targretin.

II. To determine the time to objective response in subjects with CTCL treated with dose-adjusted schedule of Vorinostat as primary therapy.

III To determine the duration of objective response in subjects with CTCL.

IV. To determine the time to loss of objective response.

V. To determine the objective response rate of extracutaneous manifestations of CTCL (lymph node enlargement, Sezary cells in peripheral blood).

VI. To compare the efficacy, toxicity and tolerability of dose-adjusted schedule to currently recommended flat dose of Vorinostat in subjects with CTCL.

OUTLINE: Patients are assigned to 1 of 2 treatment arms according to age (< 65 vs >= 65 years old).

COHORT I (>= 65 years old): Patients receive 200 mg vorinostat orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

COHORT II (< 65 years old): Patients receive 400 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 30 days.

  Eligibility

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

Inclusion Criteria:

  • Males or non-pregnant females
  • Histologically confirmed diagnosis of CTCL, including mycosis fungoides and/or Sezary syndrome
  • Documentation of diagnosis by histologic examination should be available
  • Subjects with CTCL stages IB, IIA, IIB, III, or IVA who have not received any prior systemic therapies
  • Anticipated life expectancy greater than 6 months
  • Performance status 0, 1, or 2 by Eastern Cooperative Oncology Group (ECOG) criteria
  • Written informed consent to participate in the study
  • Absolute neutrophil count (ANC) >= 1,000/mcL
  • Platelets >= 75,000/mcL
  • Hemoglobin >= 9 g/dL
  • Prothrombin time or international normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
  • Partial thromboplastin time (PTT) =< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation
  • Serum creatinine =< 1.5 X ULN OR calculated creatinine clearance >= 60 mL/min for patients with creatinine levels > 1.5 X institutional ULN; creatinine clearance should be calculated per institutional standard
  • Serum total bilirubin =< 2 X ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic aminotransaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic aminotransaminase [SGPT]) =< 3.0 X ULN
  • Alkaline Phosphatase (liver fraction) =< 3.0 X ULN

Exclusion Criteria:

  • Proven or suspected extracutaneous visceral CTCL involvement (M1) (CTCL stage IVB)
  • Presence of lymphadenopathy is permitted
  • ECOG performance status > 2
  • Concomitant use of any anti-cancer therapy or immune modifier
  • Concomitant use of any investigational agent or device
  • Concomitant therapy with any other anti-CTCL therapy, or radiation therapy (topical corticosteroids or low dose oral corticosteroids [=< 10 mg/day prednisone or equivalent] will not be excluded, but if used, the dose and schedule must be stable during the two weeks immediately prior to study entry)
  • Use of any previous systemic therapy (except single agent targretin), total skin electron beam (TSEB) therapy or extracorporeal photopheresis
  • Evidence of clinically significant (uncontrolled) hypo- or hyperthyroidism
  • Poorly controlled diabetes mellitus as evidenced by hemoglobin (Hgb)A1c > 6.5 mg/dl
  • Recent (in the past 6 months) medically significant cardiac event (i.e. myocardial infarction, cardiac surgery)
  • Presence of congestive heart failure (New York Heart Association [NYHA] class IV) or angina (NYHA class IV) or presence of a medically significant arrhythmia
  • Congenital long QT syndrome
  • Corrected QT interval > 480 msec on screening electrocardiogram (ECG)
  • Presence of uncontrolled hypertension manifested by systolic blood pressure >= 180 mmHg and/or diastolic blood pressure >= 100 mmHg
  • Documented current active infection with human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, and/or cytomegalovirus (CMV)
  • Presence of uncontrolled bacterial or viral infection (subject may be receiving chronic antimicrobial therapy)
  • History of culture-documented bacteremia in the previous 2 weeks
  • Concurrent therapy with any histone deacetylase (HDAC)-like compound; patients treated with valproic acid for epilepsy may enroll after a 30 day washout period
  • Recent change (in the past 2 weeks) in the doses or regimens of medication used for any chronic non-oncologic conditions for reasons of worsening of chronic illness (change in doses of chronic medications associated with improvement in a chronic illness are not exclusion criteria)
  • Presence of any acute or chronic non-oncologic disease which, in the opinion of the investigator, is medically uncontrolled
  • History of a prior malignancy with the exception of cervical intraepithelial neoplasia; non-melanoma skin cancer; adequately treated localized prostate carcinoma with prostate specific antigen (PSA) < 1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, and/or who is deemed at low risk for recurrence (< 30% probability) by his/her treating physician
  • Patient with a "currently active" second malignancy, other than nonmelanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled
  • Any significant medical or psychiatric condition that, in the opinion of the investigator, might prevent the subject from complying with all required study procedures
  • Women of childbearing potential must have a pregnancy test within 28 days prior to registration, and must use an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 3 months after the study
  • Females of childbearing potential and sexually active males, if indicated, must be willing and able to use two methods of contraception that are adequate to prevent or minimize risk of pregnancy for the duration of the study; one of which must be a barrier method
  • Patient has symptomatic ascites or pleural effusion (a patient who is clinically stable following treatment for these conditions is eligible)
  • Patient has had allogeneic transplant
  • Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00958074

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Andrei R. Shustov    206-288-6739      
Principal Investigator: Andrei R. Shustov         
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Andrei Shustov Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT00958074     History of Changes
Other Study ID Numbers: 6914, NCI-2009-01231
Study First Received: August 10, 2009
Last Updated: September 20, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Mycoses
Mycosis Fungoides
Lymphoma
Lymphoma, Non-Hodgkin
Sezary Syndrome
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Vorinostat
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014