Everolimus in Treating Cutaneous T-cell Lymphoma
Condition: Cutaneous T-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous
Intervention: Everolimus
Intervention description: The study drug everolimus will be self-administered (by the patients themselves). The investigator will instruct the patient to take the study drug exactly as specified in the protocol. Everolimus should be administered orally once daily, preferably in the morning, at the same time every day with our without food. Everolimus tablets should be swallowed whole with a glass of water. The tablets must not be chewed or crushed.
Everolimus will be administered orally as once daily dose of 10 mg continuously from study day 1 until progression of disease or unacceptable toxicity.
If vomiting occurs, no attempt should be made to replace the vomited dose. All dosages prescribed and dispensed to the patient and all dose changes during the study must be recorded.
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      CTCL is a rare form of lymphoma of the skin. While early stages are usually confined to the
      skin, later stages may spread to blood, lymph nodes and other organs. At this point, patients
      usually require systemic chemo. This study will investigate the effect of everolimus as
      treatment for recurrent or refractory CTCL. Participation in this study will last as long as
      the study doctor believes disease has not gotten worse, and patients continue to tolerate the
      study medication for a maximum of 1 year. Once off the treatment, patients will be followed
      for two years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Clinically and histologically confirmed diagnosis of CTCL (at least stage IB for
             mycosis fungoides and Sézary syndrome, and T2 and/or refractory to at least one prior
             treatment for CTCL other than mycosis fungoides/Sézary syndrome)

          -  Relapsed or refractory disease after at least one standard systemic treatment
             including extracorporeal photopheresis (ECP), oral bexarotene, interferon, HDAC
             inhibitors

          -  ≥18 years old

          -  WHO performance status ≤ 2

          -  Life expectancy ≥ 6 months

          -  ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL

          -  Serum bilirubin ≤ 1.5 x ULN

          -  ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)

          -  INR ≤1.5 (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin
             or on a stable dose of LMW heparin for >2 weeks at time of randomization)

          -  Serum creatinine ≤ 1.5 x ULN

          -  Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L

          -  Fasting triglycerides ≤ 2.5 x ULN.

        Exclusion Criteria:

          -  Patients currently receiving anticancer therapies or who have received anticancer
             therapies within 4 weeks of stating study drug

          -  Treatment with any investigational drug within the past 4 weeks

          -  Patients, who have had major surgery or significant traumatic injury within 4 weeks of
             starting study drug, patients who have not recovered from the side effects of any
             major surgery, or patients that may require major surgery during the study

          -  Patients receiving chronic, systemic treatment with corticosteroids or any
             immunosuppressive agent other than topical or inhaled corticosteroids

          -  Patients receiving immunization with attenuated live vaccines within one week of study
             entry or during study period

          -  Uncontrolled brain or leptomeningeal metastases, including patients who continue to
             require glucocorticoids for brain or leptomeningeal metastases

          -  Other malignancies within the past 3 years except for adequately treated carcinoma of
             the cervix or basal or squamous cell carcinomas of the skin.

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study such as:

          -  Symptomatic congestive heart failure of New York heart Association Class III or IV

          -  unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction
             within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any
             other clinically significant cardiac disease

          -  severely impaired lung function as defined as spirometry and DLCO that is 50% of the
             normal predicted value and/or O2 saturation that is 88% or less at rest on room air

          -  uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN (Note: Optimal
             glycemic control should be achieved before starting trial therapy.)

          -  active (acute or chronic) or uncontrolled severe infections

          -  liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).

          -  A known history of HIV seropositivity

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of everolimus

          -  Patients with an active, bleeding diathesis

          -  Female patients who are pregnant or breast feeding, or adults of reproductive
             potential who are not using effective birth control methods. Adequate contraception
             must be used throughout the trial and for 8 weeks after the last dose of study drug,
             by both sexes.

          -  Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate
             contraception, during the study and for 8 weeks after the end of treatment

          -  Patients who have received prior treatment with an mTOR inhibitor

          -  Patients with a known hypersensitivity to everolimus or other rapamycins or to its
             excipient

          -  History of noncompliance to medical regimens

          -  Patients unwilling to or unable to comply with the protocol