Multicenter Phase II Study to Evaluate the Clinical Activity and the Safety Profile of Everolimus in Marginal Zone B-cell Lymphomas (MZL)

• Everolimus (Drug): Everolimus (tablets, 5 mg) is given orally at the dose of 10 mg/day from day 1 to day 28 of each cycle for up to a total of 6 cycles or until progression. Patients with CR or PR may continue treatment until PD if well tolerated

Primary outcomes

• Total Body CT-Scan [Every 12 weeks]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Histologically proven diagnosis of marginal zone B-cell lymphoma relapsing/refractory following at least 1 prior systemic treatment (chemotherapy and or monoclonal antibodies).
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 symptoms.
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 months thereafter.
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.

Exclusion Criteria:

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 disease).
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.

• Emanuele Zucca, MD, Study chair, IOSI
• Annarita Conconi, MD, Study chair, AOU Maggiore della Carità Novara

NIH grants: 2009