Phase I trial of fludarabine, bortezomib and rituximab for relapsed and refractory indolent and mantle cell non-Hodgkin lymphoma.
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.
Barr
Paul M
PM
Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH 44106, USA. paul.barr@case.edu
Fu
Pingfu
P
Lazarus
Hillard M
HM
Horvath
Nancy
N
Gerson
Stanton L
SL
Koc
Omer N
ON
Bahlis
Nizar J
NJ
Snell
Michael R
MR
Dowlati
Afshin
A
Cooper
Brenda W
BW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009894:Opportunistic Infections / Q000139:chemically induced; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib; D014740:Vidarabine; C024352:fludarabine