Clarithromycin + Lenalidomide Combination: a Full Oral Treatment for Patients With Relapsed/Refractory Extranodal Marginal Zone Lymphoma

NCT03031483 | Completed Phase 2

• 1 other identifier: IELSG40
• Study Type: interventional
• Target: 44
• Locations: 3 countries
• Sites: 10

Brief Summary

Patients with lymphoid tissue lymphoma mucosa-associated (MALT) for which the standard treatments with radiotherapy, chemotherapy and / or immunotherapy show lack of efficacy

Conditions

Mucosa Associated Lymphoid Tissue (MALT) Lymphoma

Outcome Measures

Primary Outcomes (1)

• Tumor response assessment

  The primary outcome measure is tumour response assessed according to the Revised Response Criteria for Malignant Lymphoma, either clinically (including appropriate imaging procedures) or endoscopically and histologically (in patients affected by gastric lymphoma, according to the GELA scoring system).

  During the active treatment period after the 3rd cycles of both drugs administration

Secondary Outcomes (1)

• Adverse Events assessments

  During the active treatment period

Study Arms (1)

Experimental: clarithromycin and lenalidomide

EXPERIMENTAL

CLARITHROMYCIN: daily orally administration in cycles of 28 days; 500mg film-coated tablets LENALIDOMIDE: every cycle of treatment lasts 28 days; daily orally administration is of 21 consecutive days with a week of rest. 20mg capsule hard. The maximum treatment duration is 12 months.

Drug: clarithromycin and lenalidomide

Interventions

clarithromycin and lenalidomide DRUG

Each treatment course will consist of: Oral Lenalidomide (Revlimid) once daily for 21 days at a dose 20 mg; in case of drug-related adverse events the dose can be reduced to 15 and 10 mg/day; Oral Clarithromycin 500 mg twice daily for 28 days. Courses will be repeated every 28 days. After the first 3 courses patients with stable disease or better response will be given another three courses. Patients with complete remission or disease progression after 6 courses will be taken off study, while patients with partial response or stable disease will receive 3 further courses of treatment. Again, patients with complete response or disease progression will stop therapy, while patients with partial response/stable disease will receive 3 further courses up to a maximum of 12 courses in total.

Experimental: clarithromycin and lenalidomide

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically verified diagnosis of MALT lymphoma arising at any extranodal site
• Disease refractory to or in first or greater relapse after prior radiotherapy and/ or chemotherapy and/or immunotherapy
• Measurable or non-measurable lesions where the response is nevertheless evaluable by non-imaging means (e.g., gastric or bone marrow infiltrations)
• Ann Arbor Stage I-IV
• ECOG performance status of 0, 1 or 2
• Age ≥ 18 years
• Life expectancy of at least 3 months
• Adequate haematological status: ANC (absolute neutrophil count \[segmented + bands\]) ≥1.0 x 109/L, platelet count ≥ 75 x 109/L , haemoglobin ≥8 g/dL.
• Adequate cardiac, renal and liver function tests (LVEF \> 40%, serum creatinine \< 2.5 mg/dl, ALAT or ASAT \< 2.5 x upper limit of normal range, alkaline phosphatase \< 2.5 x upper limit of normal range, serum bilirubin \< 2.0 mg/dl)
• Patient must be willing and able to comply with the protocol for the entire study duration
• Female patients of childbearing potential must agree to use, and be able to comply with, effective contraception and agree to have medically supervised pregnancy tests prior to starting the study treatment and during therapy
• Male patients must agree to always use a condom during any sexual contact with females of reproductive potential and agree to not donate sperm while taking lenalidomide
• Patient must agree to abstain from donating blood while taking study drug therapy
• Patient must agree not to share study medication with another person and to return all unused study drug to the investigator
• Patient must be willing and able to comply with the protocol

You may not qualify if:

• Lymphoma histology other than MALT lymphoma or MALT lymphoma with a diffuse large cell lymphoma ("high grade lymphoma") component
• Use of any investigational agent within 28 days prior to initiation of treatment
• History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix within the last 5 years unless in complete remission since at least 3 years
• Dependency on red blood cell and/or platelet transfusions
• HBsAg positivity
• Evidence of central nervous system involvement
• A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs
• Severe peripheral polyneuropathy
• Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months and/or long QT-syndrome
• HIV seropositivity
• Presence of active opportunistic infections
• Pregnancy or lactation
• Uncontrolled diabetes mellitus
• Pre-existing thromboembolic conditions at study entry
• Known hypersensitivity to thalidomide or lenalidomide or macrolide antibiotics

Sponsors & Collaborators

• International Extranodal Lymphoma Study Group (IELSG): lead

Study Sites (10)

Medical University of Vienna

Vienna, Austria

Location

A.O. Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Azienda Ospedaliera Papardo

Messina, 98158, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Ospedale di Circolo e Fondazione Macchi di Varese

Varese, 21100, Italy

Location

Azienda Sanitaria ULSS 6 - Ospedale S.Bortolo

Vicenza, 36100, Italy

Location

Instituto de Enfermedades Hematológicas y Oncológicas

Barcelona, Barcellona, 08036, Spain

Location

Institut Català D'Oncologia Hospital Duran I Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario

Salamanca, 37007, Spain

Location

Related Publications (1)

• Pirosa MC, Sassone M, Kiesewetter B, Guillermo AL, Devizzi L, Domenech ED, Tucci A, Mannina D, Merli M, Salar A, Visco C, Esposito F, Bonomini L, Zucca E, Ferreri AJM, Raderer M. IELSG40/CLEO phase II trial of clarithromycin and lenalidomide in relapsed/refractory extranodal marginal zone lymphoma. Haematologica. 2023 Jun 1;108(6):1671-1675. doi: 10.3324/haematol.2022.281963. No abstract available.

  PMID: 36546422 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

Clarithromycin; Lenalidomide

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)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Emanuele Zucca, Prof

  International Extranodal Lymphoma Study Group

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 23, 2017
• First Posted: January 25, 2017
• Study Start: April 3, 2017
• Primary Completion: November 13, 2019
• Study Completion: December 20, 2024
• Last Updated: January 30, 2025

Record last verified: 2025-01

Locations

ES (3); AU (1); IT (6)