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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01164267
Recruitment Status : Completed
First Posted : July 16, 2010
Last Update Posted : November 25, 2013
Information provided by (Responsible Party):
International Extranodal Lymphoma Study Group (IELSG)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Marginal Zone B-cell Lymphoma Drug: Everolimus Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : March 2010
Actual Primary Completion Date : December 2012

Intervention Details:
    Drug: Everolimus
    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 Outcome Measures :
  1. Total Body CT-Scan [ Time Frame: Every 12 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01164267

General Hospital AKH
Vienna, Austria
Policlinico S. Orsola Malpighi
Bologna, Italy
Milano, Italy
Milano, Italy
Milan, Italy
San Raffaele Hospital
Milan, Italy
AOU Maggiore della Carità
Novara, Italy
IRCCS Policlinico S. Matteo
Pavia, Italy
AOU S. Giovanni Battista
Torino, Italy
Bellinzona, Switzerland
Sponsors and Collaborators
International Extranodal Lymphoma Study Group (IELSG)
Study Chair: Emanuele Zucca, MD IOSI
Study Chair: Annarita Conconi, MD AOU Maggiore della Carità Novara

Additional Information:
Responsible Party: International Extranodal Lymphoma Study Group (IELSG) Identifier: NCT01164267     History of Changes
Other Study ID Numbers: IELSG 34
2009-011725-14 ( EudraCT Number )
First Posted: July 16, 2010    Key Record Dates
Last Update Posted: November 25, 2013
Last Verified: May 2012

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents