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Clinical Trial
. 2009 Oct;147(1):89-96.
doi: 10.1111/j.1365-2141.2009.07836.x. Epub 2009 Jun 29.

Phase I trial of fludarabine, bortezomib and rituximab for relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma

Paul M Barr  1 , Pingfu Fu, Hillard M Lazarus, Nancy Horvath, Stanton L Gerson, Omer N Koc, Nizar J Bahlis, Michael R Snell, Afshin Dowlati, Brenda W Cooper
Affiliations
Clinical Trial

Phase I trial of fludarabine, bortezomib and rituximab for relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma

Paul M Barr et al. Br J Haematol. 2009 Oct.

Abstract

Based on the hypothesis that bortezomib may potentiate fludarabine activity by inhibiting DNA repair, we designed a phase I trial using this combination with rituximab in patients with relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma. Twenty-four patients were enrolled. Non-Hodgkin lymphoma subtypes included 12 patients with follicular lymphoma, four with marginal zone lymphoma, three with lymphoplasmacytic lymphoma, three with mantle cell lymphoma and two with small lymphocytic/chronic lymphocytic leukaemia. Fludarabine and bortezomib were escalated in cohorts of three patients. Rituximab was added to the maximum tolerated dose of fludarabine and bortezomib and added significant dose-limiting myelosuppression. The maximum tolerated dose was fludarabine 25 mg/m(2) on days 1-3, bortezomib 1.3 mg/m(2) on days 1, 4, 8, 11, with rituximab 375 mg/m(2) on day 1 administered every 21 d. Clinical responses were observed in 11 patients, five of whom were refractory to their most recent treatment regimen. Six additional patients had stable disease for a median of 10 months (range 4-30+). Cumulative myelosuppression and neuropathy was observed. The combination of fludarabine, bortezomib, and rituximab appears to be an active regimen with manageable toxicity for relapsed NHL.

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Conflict of interest statement

Disclosures: Consultant (PMB) for Millennium. Honoraria (NJB) from Millennium and (HML) from Genentech.

Comment in

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