A Study to Compare Subcutaneous Versus Intravenous MabThera (Rituximab) in Combination With Chemotherapy in Patients With Chronic Lymphocytic Leukemia

Summary

This randomized, parallel-group, multi-center study will compare the pharmacokinetics and safety of subcutaneous administration of MabThera (rituximab) versus intravenous MabThera in combination with chemotherapy in previously untreated patients with chronic lymphocytic leukemia (CLL). The study consists of 2 parts. In part 1, patients who have previously received 4 cycles of intravenous MabThera will receive in Cycle 5 intravenous MabThera and in Cycle 6 subcutaneous MabThera. In part 2, patients will be randomized to receive either 6 cycles of intravenous MabThera, or 1 cycle of intravenous MabThera and 5 cycles of subcutaneous MabThera. Additionally, all patients will receive chemotherapy (fludarabine and cyclophosphamide) on Days 1-3 or Days 1-5 of every cycle. The anticipated time on study drug is 24 weeks.

Timeline

Start

2011-04-18

Primary completion

2014-05-07

Completion

2017-11-17

Outcome

Met primary endpoint

paper At cycle five, the geometric mean trough serum concentration in patients given subcutaneous rituximab was non-inferior to that in patients given intravenous rituximab PMID 26947201 ↗

registry Adjusted geometric mean ratio 1.533 (90% CI 1.269 to 1.852) NCT01292603 ↗

Publications

• Assouline S, Buccheri V, Delmer A, Gaidano G, Trneny M, Berthillon N, Brewster M, Catalani O, Li S, McIntyre C, Sayyed P, Badoux X. Pharmacokinetics, safety, and efficacy of subcutaneous versus intravenous rituximab plus chemotherapy as treatment for chronic lymphocytic leukaemia (SAWYER): a phase 1b, open-label, randomised controlled non-inferiority trial. Lancet Haematol. 2016 Mar;3(3):e128-38. doi: 10.1016/S2352-3026(16)00004-1.
• Assouline S, Buccheri V, Delmer A, Gaidano G, McIntyre C, Brewster M, Catalani O, Hourcade-Potelleret F, Sayyed P, Badoux X. Pharmacokinetics and safety of subcutaneous rituximab plus fludarabine and cyclophosphamide for patients with chronic lymphocytic leukaemia. Br J Clin Pharmacol. 2015 Nov;80(5):1001-9. doi: 10.1111/bcp.12662. Epub 2015 Jul 29.
• Mao CP, Brovarney MR, Dabbagh K, Birnbock HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013 Nov 12;8(11):e80533. doi: 10.1371/journal.pone.0080533. eCollection 2013.
• Shpilberg O, Jackisch C. Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase. Br J Cancer. 2013 Sep 17;109(6):1556-61. doi: 10.1038/bjc.2013.371. Epub 2013 Sep 3.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Rituximab	Monoclonal antibody	500 mg/m2	Intravenous
Subject	Rituximab	Monoclonal antibody	1400 mg	Intravenous
Subject	Rituximab	Monoclonal antibody	1600 mg	Intravenous
Subject	Rituximab	Monoclonal antibody	1870 mg	Intravenous
Background	Cyclophosphamide	Other / unclassified	—	Oral
Background	Fludarabine	Small molecule	—	Oral

Indications