A Multicenter, Open-label, Randomized, Phase I/II Study Evaluating the Safety and Efficacy of Low-dose (12 Gy) Total Skin Electron Beam Therapy (TSEBT) Combined With Vorinostat Versus Low-dose TSEBT Monotherapy in Mycosis Fungoides (MF)
A patient will be eligible for inclusion only if all of the following criteria apply:
1. Biopsy-confirmed mycosis fungoides, clinical stage IB-IIIB.
2. Patients must have failed or have been intolerant to at least one prior systemic or
skin-directed therapy. This may include topical steroids if used as primary therapy
3.18 years of age or older.
4.Eastern Cooperative Oncology Group (ECOG) of <= 2.
5.Adequate bone marrow function: WBC > 2000/uL; platelet count > 75,000/mm3; ANC > 1000.
Patients cannot be using colony stimulating factors.
6.Required wash out period for prior therapies
- Topical therapy: 2 weeks
- Systemic biologic, monoclonal antibody, or chemotherapy: 4 weeks
- Phototherapy or radiotherapy (excluding TSEBT): 4 weeks
- Other investigational therapy: 4 weeks
- Note: patients with rapidly progressive disease may be treated earlier than required
washout period; however, such circumstance must be discussed and approved by the
protocol director at the primary site (Stanford).
7.Women of child-bearing potential (WOCBP) must have negative serum pregnancy test.
8.WOCBP must agree to use effective contraception, defined as oral contraceptives,
intrauterine devices, double barrier method (condom plus spermicide or diaphragm) or
abstain from sexual intercourse. WOCBP includes any female who has experienced
menarche and who has not undergone successful surgical sterilization or is not
postmenopausal (defined as amenorrhea for 12 consecutive months).
9.Male subjects must be willing to use an appropriate method of contraception (e.g.,
condoms) or abstain from sexual intercourse and inform any sexual partners that they
must also use a reliable method of contraception (e.g., birth control pills) during
10.Adequate hepatic function: bilirubin <= 1.5 x upper limit of normal (ULN), AST <=
2.5 x UNL, ALT <= 2.5 x UNL, alkaline phosphatase (liver fraction) <= 2.5 x ULN
11.Adequate renal function: creatinine <=1.5 x UNL OR creatinine clearance <=60
mL/min for patients with creatinine levels > 1.5 X institutional ULN
12.Metabolic parameters: potassium level between 3.5 and 4.5, magnesium level between
1.5 and 2.5
13.Ability to understand and sign a written informed consent document.
14.Ability to comply with the treatment schedule
A patient will not be eligible for inclusion if any of the following criteria apply:
1. Prior courses of TSEBT (Note: localized skin-directed radiotherapy is allowed if
administered at least 4 weeks prior to initiation on study).
2. Concomitant use of any anti-cancer therapy or immune modifier.
3. Prior allogeneic or autologous transplant.
4. Active infection or have received intravenous antibiotics, antiviral, or antifungal
agents within 2 weeks prior to the start of the study drug.
5. Known history of human immunodeficiency virus (HIV), hepatitis B or C.
6. History of prior malignancy with the exception of cervical intraepithelial neoplasia,
non-melanoma skin cancer, and adequately treated localized prostate carcinoma (PSA
<1.0). Patients with a history of other malignancies must have undergone potentially
curative therapy and have no evidence of that disease for five years.
7. Patient has uncontrolled intercurrent illness, condition, or circumstances that could
limit compliance with the study, including, but not limited to the following: active
infection, acute or chronic graft versus host disease, symptomatic congestive heart
failure, unstable angina pectoris, medically significant cardiac arrhythmia,
uncontrolled diabetes mellitus or hypertension, or psychiatric conditions.
8. Recent (in the past 6 months) medically significant cardiac event (i.e. myocardial
infarction, cardiac surgery.
9. Congenital long QT syndrome.
10. QTc interval > 480 msec on screening ECG.
11. Proven or suspected stage IV disease including patients with B2 (Sezary syndrome), N3
(frank LN disease), or M1 (visceral disease) categories; presence of reactive or
dermatopathic lymphadenopathy (N1-2) or limited blood involvement (B1) is permitted.
12. ECOG performance status >2.
13. Pregnant or lactating.
14. Unwilling to use reliable birth control methods.
15. Any other medical issue, including laboratory abnormalities, deemed by the
Investigator to be likely to interfere with patient participation.
16. Unwilling or unable to provide informed consent.