Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, Previously untreated chronic lymphocytic leukemia

Blood

Volumn 127, Issue 1, 2016, Pages 79-86

  Byrd, John C ^a,b   Flynn, Joseph M ^a   Kipps, Thomas J ^c   Boxer, Michael ^d,e   Kolibaba, Kathryn S ^e,f   Carlile, David J ^g   Fingerle Rowson, Guenter ^h   Tyson, Nicola ^g   Hirata, Jamie ⁱ   Sharman, Jeff P ^e,j  

^a Division of Hematology and Comprehensive Cancer Center   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^d Arizona Oncology Associates   (United States)

^e US Oncology Research   (Canada)

^f Northwest Cancer Specialists   (Canada)

^g ROCHE PRODUCTS LTD   (United Kingdom)

^h F HOFFMANN LA ROCHE LTD   (Switzerland)

ⁱ GENENTECH INC   (United States)

^j US Oncology Research Willamette Valley Cancer Institute   (United States)

more..

Author keywords

But no difference in progression Free survival; No meaningful difference was observed in the overall safety profile across the 2 treatment arms; Obinutuzumab monotherapy demonstrates an increased ORR with 2000 mg over 1000 mg

Indexed keywords

OBINUTUZUMAB; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY;

ACUTE CORONARY SYNDROME; ADULT; AGED; ARTICLE; BODY TEMPERATURE DISORDER; CHILL; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; COUGHING; CYTOPENIA; DIZZINESS; DOSE RESPONSE; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FEVER; FLUSHING; HEADACHE; HUMAN; HYPOTENSION; HYPOXIA; INFUSION RELATED REACTION; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; THROMBOCYTOPENIA; TREATMENT RESPONSE; TUMOR LYSIS SYNDROME; VOMITING; CANCER STAGING; CLINICAL TRIAL; FOLLOW UP; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MIDDLE AGED; MORTALITY; PATHOLOGY; PROGNOSIS; REMISSION; SURVIVAL RATE; TISSUE DISTRIBUTION; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; FEMALE; FOLLOW-UP STUDIES; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MIDDLE AGED; NEOPLASM STAGING; PROGNOSIS; REMISSION INDUCTION; SURVIVAL RATE; TISSUE DISTRIBUTION;

EID: 84955484673     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2015-03-634394     Document Type: Article

References (28)

1. Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343(24):1750-1757.
2. Eichhorst BF, Busch R, Stilgenbauer S, et al; German CLL Study Group (GCLLSG). First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009;114(16): 3382-3391.
3. Catovsky D, Richards S, Matutes E, et al; UK National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): A randomised controlled trial. Lancet. 2007; 370(9583):230-239.
4. Flinn IW, Neuberg DS, Grever MR, et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007;25(7):793-798.
5. Eichhorst BF, Busch R, Hopfinger G, et al; German CLL Study Group. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006;107(3): 885-891.
6. Byrd JC, Peterson BL, Morrison VA, et al. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood. 2003;101(1):6-14.
7. Byrd JC, Rai K, Peterson BL, et al. Addition of rituximab to fludarabine may prolong progressionfree survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: An updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood. 2005;105(1):49-53.
8. Keating MJ, O'Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005;23(18):4079-4088.
9. Hallek M, Fischer K, Fingerle-Rowson G, et al; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: A randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164-1174.
10. McLaughlin P, Grillo-L opez AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16(8):2825-2833.
11. O'Brien SM, Kantarjian H, Thomas DA, et al. Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol. 2001;19(8): 2165-2170.
12. Byrd JC, Murphy T, Howard RS, et al. Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol. 2001;19(8):2153-2164.
13. O'Brien S, Wierda WG, Faderl S, et al. FCR-3 as frontline therapy for patients with chronic lymphocytic leukemia (CLL) [abstract]. Blood. 2005;106(11). Abstract 2117.
14. Wierda WG, Kipps TJ, Mayer J, et al; Hx-CD20- 406 Study Investigators. Ofatumumab as single-agent CD20 immunotherapy in fludarabinerefractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28(10):1749-1755.
15. Wierda WG, Padmanabhan S, Chan GW, Gupta IV, Lisby S, Osterborg A; Hx-CD20-406 Study Investigators. Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study. Blood. 2011;118(19): 5126-5129.
16. Rafiq S, Butchar JP, Cheney C, et al. Comparative assessment of clinically utilizedCD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties. J Immunol. 2013;190(6):2702-2711.
17. Flinn IW, Harwin WN, Ward P, et al. Phase II trial of ofatumumab (OFA) for older patients and patients who refuse fludarabine-based regimens with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) [abstract]. Blood. 2012;120(21). Abstract 719.
18. Mossner E, Brunker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cellmediated B-cell cytotoxicity. Blood. 2010;115(22): 4393-4402.
19. Patz M, Isaeva P, Forcob N, et al. Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells. Br J Haematol. 2011;152(3): 295-306.
20. Alduaij W, Ivanov A, Honeychurch J, et al. Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies. Blood. 2011;117(17):4519-4529.
21. Herter S, Herting F, Mundigl O, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013;12(10):2031-2042.
22. Cartron G, de Guibert S, Dilhuydy MS, et al. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014;124(14): 2196-2202.
23. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101-1110.
24. Hallek M, Cheson BD, Catovsky D, et al; International Workshop on Chronic Lymphocytic Leukemia. 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 [published correction appears in Blood. 2008;112(13):5259]. Blood. 2008;111(12):5446-5456.
25. Gibiansky E, Gibiansky L, Carlile DJ, Jamois C, Buchheit V, Frey N. Population pharmacokinetics of obinutuzumab (GA101) in chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma and exposure-response in CLL. CPT Pharmacometrics Syst Pharmacol. 2014;3(10):e144.
26. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000; 343(26):1910-1916.
27. Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32-42.
28. Brown JR, Byrd JC, Coutre SE, et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110d, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014;123(22):3390-3397.