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

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

This is a multicenter open-label uncontrolled phase II study. There are no previous clinical data to estimate the expected response rate of everolimus in MALT lymphomas and in the other less common MZLs (i.e. nodal and splenic) refractory or relapsing after at least 1 prior systemic treatment (chemotherapy or immunotherapy).

The primary objective of this study is to define the antitumor activity, in term of overall response rate (ORR), as sum of complete remissions (CR) and partial remissions (PR) of everolimus in relapsed or refractory marginal zone B-cell lymphomas.

The secondary objectives of this study are to assess safety, as acute or long-term toxicity, response duration (RD) (time to relapse or progression) in responders and progression-free survival (PFS) (time to disease progression or death from any cause) in all patients.

Study Overview

• Status: Completed
• Conditions: Marginal Zone B-cell Lymphoma
• Intervention / Treatment: Drug: Everolimus

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • General Hospital AKH
• Italy
  • Bologna, Italy
    • Policlinico S. Orsola Malpighi
  • Milan, Italy
    • Humanitas
  • Milan, Italy
    • San Raffaele Hospital
  • Milano, Italy
    • IEO
  • Milano, Italy
    • INT
  • Novara, Italy
    • AOU Maggiore della Carità
  • Pavia, Italy
    • IRCCS Policlinico S. Matteo
  • Torino, Italy
    • AOU S. Giovanni Battista
• Switzerland
  • Bellinzona, Switzerland
    • IOSI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total Body CT-Scan	Every 12 weeks

Collaborators and Investigators

• Sponsor: International Extranodal Lymphoma Study Group (IELSG)
• Investigators: Study Chair: Emanuele Zucca, MD, IOSI; Study Chair: Annarita Conconi, MD, AOU Maggiore della Carità Novara

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 15, 2010
• First Submitted That Met QC Criteria: July 15, 2010
• First Posted (Estimate): July 16, 2010

Study Record Updates

• Last Update Posted (Estimate): November 25, 2013
• Last Update Submitted That Met QC Criteria: November 21, 2013
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: IELSG 34; 2009-011725-14 (EudraCT Number)