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

NCT ID: NCT03031483

Last Updated: 2025-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-03
• Study Completion Date: 2024-12-20

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental: clarithromycin and lenalidomide

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.

Group Type: EXPERIMENTAL

clarithromycin and lenalidomide

Intervention Type: 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.

Interventions

clarithromycin and lenalidomide

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• Patient must be capable of understanding

Exclusion Criteria

• 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
• Presence of any contraindication reported on the Summary of Product Characteristics (SmPC) of Clarithromycin
• Hypersensitivity to any active principle and/or any excipient according to the contraindications reported in the SmPC of clarithromycin and in the Investigator's Brochure (IB) of lenalidomide

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

International Extranodal Lymphoma Study Group (IELSG)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emanuele Zucca, Prof

Role: STUDY_DIRECTOR

International Extranodal Lymphoma Study Group

Locations

Medical University of Vienna

Vienna, , Austria

A.O. Spedali Civili di Brescia

Brescia, , Italy

Azienda Ospedaliera Papardo

Messina, , Italy

IRCCS Ospedale San Raffaele

Milan, , Italy

Fondazione IRCCS - Istituto Nazionale dei Tumori

Milan, , Italy

Ospedale di Circolo e Fondazione Macchi di Varese

Varese, , Italy

Azienda Sanitaria ULSS 6 - Ospedale S.Bortolo

Vicenza, , Italy

Instituto de Enfermedades Hematológicas y Oncológicas

Barcelona, Barcellona, Spain

Institut Català D'Oncologia Hospital Duran I Reynals

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario

Salamanca, , Spain

Countries

Austria; Italy; Spain

References

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.

Reference Type: DERIVED

PMID: 36546422 (View on PubMed)

Other Identifiers

IELSG40

Identifier Type: -

Identifier Source: org_study_id