Salvage Therapy With High Dose Oral Clarithromycin in Relapsed or Refractory Extranodal Marginal Zone Lymphoma

Phase II Clinical Trial on the Activity of Salvage Therapy With High Dose Oral Clarithromycin in Patients With Relapsed or Refractory Extranodal Marginal Zone Lymphoma

This is a prospective, phase II study on the activity and tolerability of high dose (2 g/day) oral clarithromycin for the treatment of relapsed or refractory extranodal marginal zone lymphoma.

A 6-month regimen of oral clarithromycin has been associated with a 35% ORR in patients with relapsed/refractory marginal zone B-cell lymphoma. Responses were more common among patients with conjunctival lymphoma. This could be explained at least in part by the elimination of clarithromycin by tears, suggesting that a higher tumor bioavailability of this antibiotic could result in a higher activity. Thus, a higher dose of clarithromycin could be associated with a higher tumor bioavailability in tissues other than the conjunctiva.

Inclusion Criteria:

• histologically confirmed diagnosis of extranodal extra-gastric marginal zone cell B lymphoma or gastric Helicobacter pylori positive lymphoma refractory to conventional antibiotic therapy, or H. pylori negative
• at least one measurable lesion
• relapsed or refractory lymphoma after systemic (chemotherapy, immunotherapy, antibiotic) or local (surgery or radiation) therapy
• ECOG PS </= 3
• no prior antibiotic therapy within 3 months before enrollment

Exclusion Criteria:

• HIV 1-2 infection
• concomitant conventional or experimental antitumor therapy (chemotherapy, radiotherapy, immunotherapy, corticosteroids)
• severe inadequate liver (AST </=3 ULN, ALT </= 3 ULN, bilirubin </=3 ULN) or renal (creatinine </= 1.5 ULN) function
• allergy to macrolides
• concomitant malignant neoplasms within prior 5 years (with the exclusion of basal cell carcinoma, in situ spinocellular carcinoma of skin and cervix)