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

A Phase II Trial Addressing Feasibility and Activity of Clarithromycin + Lenalidomide Combination: a Full Oral Treatment for Patients With Relapsed/Refractory Extranodal Marginal Zone Lymphoma

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

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