A Multicenter Phase II Study to Evaluate the Clinical Activity and the Safety Profile of Everolimus (RAD001) in Marginal Zone B-cell Lymphomas (MZL) EudraCT Number 2009-011725-14
1. Histologically proven diagnosis of marginal zone B-cell lymphoma relapsing/refractory
following at least 1 prior systemic treatment (chemotherapy and or monoclonal
2. Any stage (Ann Arbor I-IV).
3. No evidence of histologic transformation to aggressive lymphoma.
4. Measurable or evaluable disease.
5. Age > 18 years.
6. Life expectancy of at least 3 months.
7. ECOG performance status 0-1.
8. No prior diagnosis of neoplasm within 5 years, except cervical type 1 intraepithelial
neoplasia or localized non-melanomatous skin cancer.
9. In case of prior diagnosis of solid organ tumors, no treatment over the last 5 years
ond no current evidence of disease.
10. No prior chemo-or radiotherapy in the last 6 weeks, no prior immunotherapy in the
last 8 weeks, no corticosteroids during the last 4 weeks unless low-dose prednisone
chronically administered for indications other than lymphoma or lymphoma-related
11. No major impairment of bone marrow function, renal function or liver function unless
due to lymphoma.
12. No evidence of active opportunistic infections, no HIV infection, no evidence of HBV
infection, no active HCV infection.
13. Women of childbearing potential are using effective contraception, are not breast
feeding, are not pregnant and agree not to become pregnant during participation in
the trial and during the 12 months thereafter. A negative pregnancy test is mandatory
for all patients < 50 years (unless considered unnecessary by the investigator).
Men agree not to father a child during participation in the trial and during the 12
14. No serious cardiac, neurological or psychiatric disorders potentially hampering
compliance with the study protocol and follow-up schedule.
15. Fasting serum cholesterol ≤ 200 mg/dL or ≤ 5 mmol/L AND fasting triglycerides ≤ 200
mg/dL. NOTE: In case one or both of these thresholds are exceeded, the patient can
only be included after initiation of appropriate lipid lowering medication.
16. Written informed consent.
1. Patients with newly diagnosed MZL.
2. Patients with concomitant or past hematological malignancies.
3. Presence or history of CNS lymphoma localization (either parenchymal or meningeal
4. Cardiovascular disease (congestive heart failure; NYHA III or IV), unstable angina
pectoris, significant cardiac arrhythmias requiring chronic treatment, or prior
history of myocardial infarction in the last 3 months.
5. Serious underlying medical condition which could impair the ability of the patient to
participate in the trial (e.g. uncontrolled diabetes mellitus, gastric ulcers, active
autoimmune disease, ongoing infection e.g. HIV, hepatitis).
6. Concurrent anticancer drugs / treatments and experimental drugs. Previous radiation
is allowed, unless the indicator lesion(s) are in the irradiated field.
7. Previous organ transplantation
8. Participation in another clinical trial within 30 days prior to trial entry
9. Pregnant or lactating women.