Vorinostat in Patients With Primary Cutaneous T-Cell Lymphoma
Condition: Cutaneous T-cell Lymphoma Stage I; Cutaneous T-cell Lymphoma Stage II; Cutaneous T-cell Lymphoma Stage III; Cutaneous T-cell Lymphoma Stage IV
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous
Intervention: vorinostat; flow cytometry; laboratory biomarker analysis
Intervention description: Given PO; correlative study; correlative study
Intervention MeSH terms: Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility 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