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

NCT01164267 | Completed Phase 2 DMC

• 2 other identifiers: IELSG 342009-011725-14
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 10

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.

Conditions

Marginal Zone B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Total Body CT-Scan

  Every 12 weeks

Interventions

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven diagnosis of marginal zone B-cell lymphoma relapsing/refractory following at least 1 prior systemic treatment (chemotherapy and or monoclonal antibodies).
• Any stage (Ann Arbor I-IV).
• No evidence of histologic transformation to aggressive lymphoma.
• Measurable or evaluable disease.
• Age \> 18 years.
• Life expectancy of at least 3 months.
• ECOG performance status 0-1.
• No prior diagnosis of neoplasm within 5 years, except cervical type 1 intraepithelial neoplasia or localized non-melanomatous skin cancer.
• In case of prior diagnosis of solid organ tumors, no treatment over the last 5 years ond no current evidence of disease.
• 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.
• No major impairment of bone marrow function, renal function or liver function unless due to lymphoma.
• No evidence of active opportunistic infections, no HIV infection, no evidence of HBV infection, no active HCV infection.
• 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.
• No serious cardiac, neurological or psychiatric disorders potentially hampering compliance with the study protocol and follow-up schedule.

You may not qualify if:

• Patients with newly diagnosed MZL.
• Patients with concomitant or past hematological malignancies.
• Presence or history of CNS lymphoma localization (either parenchymal or meningeal disease).
• 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.
• 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).
• Concurrent anticancer drugs / treatments and experimental drugs. Previous radiation is allowed, unless the indicator lesion(s) are in the irradiated field.
• Previous organ transplantation
• Participation in another clinical trial within 30 days prior to trial entry
• Pregnant or lactating women.

Sponsors & Collaborators

• International Extranodal Lymphoma Study Group (IELSG): lead

Study Sites (10)

General Hospital AKH

Vienna, Austria

Location

Policlinico S. Orsola Malpighi

Bologna, Italy

Location

Humanitas

Milan, Italy

Location

San Raffaele Hospital

Milan, Italy

Location

IEO

Milan, Italy

Location

INT

Milan, Italy

Location

AOU Maggiore della Carità

Novara, Italy

Location

IRCCS Policlinico S. Matteo

Pavia, Italy

Location

AOU S. Giovanni Battista

Torino, Italy

Location

IOSI

Bellinzona, Switzerland

Location

Related Links

• Related Info

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Emanuele Zucca, MD

  IOSI

  STUDY CHAIR

• Annarita Conconi, MD

  AOU Maggiore della Carità Novara

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 16, 2010
• Study Start: March 1, 2010
• Primary Completion: December 1, 2012
• Last Updated: November 25, 2013

Record last verified: 2012-05

Locations

IT (8); CH (1); AU (1)