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

The Lancet Haematology

Volumn 3, Issue 3, 2016, Pages e128-e138

  Assouline, Sarit ^a   Buccheri, Valeria ^b   Delmer, Alain ^c   Gaidano, Gianluca ^d   Trneny, Marek ^e   Berthillon, Natalia ^f   Brewster, Michael ^g   Catalani, Olivier ^f   Li, Sai ^f   McIntyre, Christine ^g   Sayyed, Pakeeza ^f   Badoux, Xavier ^h  

^a MCGILL UNIVERSITY   (Canada)

^b UNIVERSITY OF SÃO PAULO   (Brazil)

^c SERVICE DE DERMATOLOGIE   (France)

^d UNIVERSITY OF EASTERN PIEDMONT   (Italy)

^e CHARLES UNIVERSITY   (Czech Republic)

^f F HOFFMANN LA ROCHE LTD   (Switzerland)

^g ROCHE PRODUCTS LTD   (United Kingdom)

^h ST GEORGE HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CD19 ANTIGEN; CYCLOPHOSPHAMIDE; FLUDARABINE; PREDNISOLONE; RITUXIMAB; ALKYLATING AGENT; ANTINEOPLASTIC AGENT; VIDARABINE;

ACUTE KIDNEY FAILURE; ANEMIA; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; B LYMPHOCYTE; BLOOD SAMPLING; BONE PAIN; CANCER CHEMOTHERAPY; CANCER STAGING; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL OUTCOME; COMPUTER ASSISTED TOMOGRAPHY; CONTROLLED STUDY; DIARRHEA; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; ELECTROCHEMILUMINESCENCE; ENZYME LINKED IMMUNOSORBENT ASSAY; ERYTHEMA; FEBRILE NEUTROPENIA; FEMALE; FEVER; FLOW CYTOMETRY; FOLLOW UP; HEMOLYTIC ANEMIA; HERPES ZOSTER; HUMAN; HYPERTENSION; HYPOTENSION; INJECTION SITE ERYTHEMA; INJECTION SITE PAIN; LEUKOPENIA; LISTERIOSIS; LYMPHOCYTE COUNT; LYMPHOCYTOPENIA; MAJOR CLINICAL STUDY; MALE; MASKING; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; OPEN STUDY; PHASE 1 CLINICAL TRIAL; PHYSICAL EXAMINATION; PNEUMONIA; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PRURITUS; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY TRACT DISEASE; RESPIRATORY TRACT INFECTION; THROMBOCYTOPENIA; UPPER RESPIRATORY TRACT INFECTION; URTICARIA; VOMITING; X-RAY COMPUTED TOMOGRAPHY; ADULT; AGED; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; CUTANEOUS DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MIDDLE AGED; MULTICENTER STUDY; TREATMENT OUTCOME;

ADMINISTRATION, CUTANEOUS; ADMINISTRATION, INTRAVENOUS; ADULT; AGED; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC AGENTS, ALKYLATING; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CYCLOPHOSPHAMIDE; FEMALE; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MIDDLE AGED; RITUXIMAB; TREATMENT OUTCOME; VIDARABINE;

EID: 85007558174     PISSN: None     EISSN: 23523026     Source Type: Journal    
DOI: 10.1016/S2352-3026(16)00004-1     Document Type: Article

References (28)

1. Hallek, M, Fischer, K, Fingerle-Rowson, G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 376 (2010), 1164–1174.
2. Rituxan prescribing information. http://www.gene.com/download/pdf/rituxan_prescribing.pdf, 2014 (accessed May 12, 2015).
3. Stilgenbauer, S, Zenz, T, Winkler, D, et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 27 (2009), 3994–4001.
4. Pivot, X, Gligorov, J, Müller, V, et al. Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHer): an open-label randomised study. Lancet Oncol 14 (2013), 962–970.
5. Rule, S, Collins, GP, Samanta, K, Subcutaneous vs intravenous rituximab in patients with non-Hodgkin lymphoma: a time and motion study in the United Kingdom. J Med Econ 17 (2014), 459–468.
6. Davies, A, Merli, F, Mihaljevic, B, et al. Pharmacokinetics and safety of subcutaneous rituximab in follicular lymphoma (SABRINA): stage 1 analysis of a randomised phase 3 study. Lancet Oncol 15 (2014), 343–352.
7. Davies A, Merli F, Mihaljevic B, et al. Subcutaneous rituximab and chemotherapy achieves similar overall response rates to intravenous rituximab in first-line follicular lymphoma: efficacy and safety results of the phase III SABRINA study. 19th Congress of the European Hematology Association; Milan, Italy; June 12–15, 2014. S652.
8. Aue, G, Lindorfer, MA, Beum, PV, et al. Fractionated subcutaneous rituximab is well-tolerated and preserves CD20 expression on tumor cells in patients with chronic lymphocytic leukemia. Haematologica 95 (2010), 329–332.
9. Hale, G, Rebello, P, Brettman, LR, et al. Blood concentrations of alemtuzumab and antiglobulin responses in patients with chronic lymphocytic leukemia following intravenous or subcutaneous routes of administration. Blood 104 (2004), 948–955.
10. Karlsson, C, Norin, S, Kimby, E, et al. Alemtuzumab as first-line therapy for B-cell chronic lymphocytic leukemia: long-term follow-up of clinical effects, infectious complications and risk of Richter transformation. Leukemia 20 (2006), 2204–2207.
11. Rummel, M, Kim, TM, Plenteda, C, et al. Patient preference for subcutaneous or intravenous administration of rituximab in previously untreated CD20+ non-Hodgkin's lymphoma: interim data from the PrefMAB study. Haematologica, 99(suppl 1), 2014, P467.
12. Bookbinder, LH, Hofer, A, Haller, MF, et al. A recombinant human enzyme for enhanced interstitial transport of therapeutics. J Control Release 114 (2006), 230–241.
13. Frost, GI, Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin Drug Deliv 4 (2007), 427–440.
14. Thomas, JR, Yocum, RC, Haller, MF, Flament, J, The INFUSE-Morphine IIB study: use of recombinant human hyaluronidase (rHuPH20) to enhance the absorption of subcutaneous morphine in healthy volunteers. J Pain Symptom Manage 38 (2009), 673–682.
15. Harb, G, Lebel, F, Battikha, J, Thackara, JW, Safety and pharmacokinetics of subcutaneous ceftriaxone administered with or without recombinant human hyaluronidase (rHuPH20) versus intravenous ceftriaxone administration in adult volunteers. Curr Med Res Opin 26 (2010), 279–288.
16. Ismael, G, Hegg, R, Muehlbauer, S, et al. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol 13 (2012), 869–878.
17. Salar, A, Avivi, I, Bittner, B, et al. Comparison of subcutaneous versus intravenous administration of rituximab as maintenance treatment for follicular lymphoma: results from a two-stage, phase IB study. J Clin Oncol 32 (2014), 1782–1791.
18. Lugtenburg, P, Rueda, A, Avivi, I, et al. Subcutaneous versus intravenous rituximab in combination with CHOP for previously untreated diffuse large B-cell lymphoma: efficacy and safety results from the phase IIIb MABEASE study. Haematologica, 100(suppl 1), 2015, S483.
19. , RB, D'Agostino Sr, Massaro, JM, Sullivan, LM, Non-inferiority trials: design concepts and issues—the encounters of academic consultants in statistics. Stat Med 22 (2003), 169–186.
20. Assouline, S, Buccheri, V, Delmer, A, et al. Pharmacokinetics and safety of subcutaneous rituximab plus fludarabine and cyclophosphamide for patients with chronic lymphocytic leukemia. Br J Clin Pharmacol 80 (2015), 1001–1009.
21. Hallek, M, Cheson, BD, Catovsky, D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 111 (2008), 5446–5456.
22. van der Velden, VH, Cazzaniga, G, Schrauder, A, et al. Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia 21 (2007), 604–611.
23. Böttcher, S, Stilgenbauer, S, Busch, R, et al. Standardized MRD flow and ASO IGH RQ-PCR for MRD quantification in CLL patients after rituximab-containing immunochemotherapy: a comparative analysis. Leukemia 23 (2009), 2007–2017.
24. Tobinai, K, Igarashi, T, Itoh, K, et al., for the IDEC-C2B8 Japan Study Group. Japanese multicentre phase II and pharmacokinetic study of rituximab in relapsed or refractory patients with aggressive B-cell lymphoma. Ann Oncol 15 (2004), 821–830.
25. Yin, A, Li, J, Hurst, D, Visich, J, Population pharmacokinetics (PK) and association of PK and clinical outcomes of rituximab in patients with non-Hodgkin's lymphoma. Proc Am Soc Clin Oncol, 28(suppl), 2010, e13108.
26. Vogel, WH, Infusion reactions: diagnosis, assessment, and management. Clin J Oncol Nurs 14 (2010), E10–E21.
27. Lundin, J, Kimby, E, Björkholm, M, et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood 100 (2002), 768–773.
28. Jackisch, C, Kim, SB, Semiglazov, V, et al. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol 26 (2015), 320–325.