Forodesine in the Treatment of Cutaneous T-Cell Lymphoma

Exclusion Criteria

• •Proven or suspected extracutaneous visceral CTCL involvement (M1) (CTCL stage IVB) (note: presence of lymphadenopathy is permitted);
• •Previous treatment with Forodesine;
• •ECOG performance status \>2;
• •Concomitant use of any anti-cancer therapy or immune modifier;
• •Concomitant use of any investigational agent or device;
• •Concurrent treatment with any other anti-CTCL therapy, or radiation therapy \[topical corticosteroids (classes 1 and 2 prohibited) or low dose oral corticosteroids (≤10 mg/day prednisone or equivalent) will not be excluded, but if used, must be a stable dose and schedule during the four weeks immediately prior to study entry\];
• •Use of previous therapies for CTCL within the timeframes specified below:
• •1. Phototherapy in the previous 30 days;
• •2. Electron beam therapy, photopheresis, systemic anticancer therapy, interferon therapy, or other investigational therapy in the previous 30 days;
• •3. Oral retinoid (including bexarotene) in the previous 30 days
• •4. Alemtuzumab (Campath) or other monoclonal antibody within the previous 30 days
• •5. Vorinostat or other HDAC inhibitor within previous 30 days
• •6. Any investigational therapy within the previous 30 days;
• •ALT or AST \>3 times ULN or alkaline phosphatase \>2 times ULN;
• •Calculated creatinine clearance ≤50 mL/min or serum creatinine ≥1.8 mg/dL;
• •Serum potassium \<3.3 mg/dL or \>5.5 mg/dL;
• •Evidence of clinically significant (uncontrolled) hypo- or hyperthyroidism;
• •Recent (in past 6 months) medically significant cardiac event (i.e., myocardial infarction, cardiac surgery);
• •Presence of congestive heart failure (NYHA class IV) or angina (NYHA class IV) or presence of a medically significant dysrhythmia;
• •Presence of any of the following ECG findings:
• •1. Congenital long QT syndrome;
• •2. QTc interval \>480 msec (Bazett's correction);
• •Presence of uncontrolled hypertension manifested by systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥90 mmHg;
• •Hemoglobin \<9.0 gm/dL (intermittent red blood cell transfusions permitted);
• •Absolute neutrophil count \<1500 cells/mm3;
• •Platelet count \<75,000/mm3;
• •Requirement for neutrophil or platelet growth factor therapy or administration of such therapy in the previous 30 days;
• •CD4 count \<200/mm3;
• •Documented current active infection with HIV, Hepatitis B, Hepatitis C, and/or CMV;
• •Presence of uncontrolled bacterial or viral infection (subject may be receiving chronic antimicrobial therapy); or,
• •History of culture-documented bacteremia in the previous 2 weeks;
• •Recent (i.e., in past 2 weeks) change in doses or regimens of medications used for any chronic non-oncologic condition for reasons of worsening of the chronic illness (change in doses of chronic medications associated with improvement in a chronic illness are not exclusionary);
• •Presence of any acute or chronic non-oncologic disease which, in the opinion of the investigator, is medically uncontrolled;
• •Coexistent second malignancy or history of prior malignancy within previous 5 years \[excluding basal cell or squamous cell carcinoma of skin and cervical neoplasia (carcinoma-in-situ) that has been treated curatively\]. Surgically resected nonmelanomatous skin cancer (non-CTCL) with no evidence of recurrence in previous 6 months is permitted; and,
• •Any significant medical or psychiatric condition that, in the opinion of the investigator, might prevent the subject from complying with all required study procedures.