Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study
Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab i...
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| creator | Burger, Jan A, Dr Keating, Michael J, Prof Wierda, William G, Prof Hartmann, Elena, MD Hoellenriegel, Julia, MS Rosin, Nathalie Y, PhD de Weerdt, Iris, MD Jeyakumar, Ghayathri, MD Ferrajoli, Alessandra, MD Cardenas-Turanzas, Marylou, PhD Lerner, Susan, MS Jorgensen, Jeffrey L, MD Nogueras-González, Graciela M, MS Zacharian, Gracy, MS Huang, Xuelin, PhD Kantarjian, Hagop, Prof Garg, Naveen, MD Rosenwald, Andreas, Prof O'Brien, Susan, Prof |
| description | Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab in patients with high-risk CLL. Methods In this single-arm phase 2 study, we enrolled adult patients with high-risk CLL at the MD Anderson Cancer Center (Houston, TX, USA). All enrolled participants had high-risk cytogenetic abnormalities (deletion 17p, TP53 mutation, or deletion 11q) or a short progression-free survival (PFS |
| doi_str_mv | 10.1016/S1470-2045(14)70335-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1566841019</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1470204514703353</els_id><sourcerecordid>3419627681</sourcerecordid><originalsourceid>FETCH-LOGICAL-c561t-d56c68f5e1c12d5ac2e6b4b3d35e8fd7a78dabca0b62696bc37ddb9f2730bd553</originalsourceid><addsrcrecordid>eNqFkctu1TAQhiMEoqXwCCBLbIpEwI4v8WEBQhU3qRKLwtryZdK4J7faTiEvwHPjnBSQumE1Y-ubf-z_L4qnBL8imIjXF4TVuKww46eEvagxpbyk94rjfM1KzqS8f-g35Kh4FOMVxqQmmD8sjipOOK538rj4daEbSAvSg0PaJn_j82FskDdhTn7wBk3dHFHwaf7pe21QMwY06eRhSBH98KlFrb9sy-DjHtk2jIO3qFv6qR3tktYe5r2G3us3SKPoh8sOSh36l2hqdQRUoZhmtzwuHjS6i_Dktp4U3z9--Hb2uTz_-unL2fvz0nJBUum4sEI2HIgllePaViAMM9RRDrJxta6l08ZqbEQldsJYWjtndk1VU2wc5_SkON10pzBezxCT6n200HV6gHGOinAhJMsG7zL6_A56Nc5hyK_LFJeSMUFkpvhG2TDGGKBRU8g-hUURrNag1CEotaagCFOHoBTNc89u1WfTg_s79SeZDLzbAMh23HgIKtpsugXnA9ik3Oj_u-LtHQXb5USt7vawQPz3GxUrhTeRVWOtWYHS34ABuVc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1558844618</pqid></control><display><type>article</type><title>Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>ProQuest Central UK/Ireland</source><creator>Burger, Jan A, Dr ; Keating, Michael J, Prof ; Wierda, William G, Prof ; Hartmann, Elena, MD ; Hoellenriegel, Julia, MS ; Rosin, Nathalie Y, PhD ; de Weerdt, Iris, MD ; Jeyakumar, Ghayathri, MD ; Ferrajoli, Alessandra, MD ; Cardenas-Turanzas, Marylou, PhD ; Lerner, Susan, MS ; Jorgensen, Jeffrey L, MD ; Nogueras-González, Graciela M, MS ; Zacharian, Gracy, MS ; Huang, Xuelin, PhD ; Kantarjian, Hagop, Prof ; Garg, Naveen, MD ; Rosenwald, Andreas, Prof ; O'Brien, Susan, Prof</creator><creatorcontrib>Burger, Jan A, Dr ; Keating, Michael J, Prof ; Wierda, William G, Prof ; Hartmann, Elena, MD ; Hoellenriegel, Julia, MS ; Rosin, Nathalie Y, PhD ; de Weerdt, Iris, MD ; Jeyakumar, Ghayathri, MD ; Ferrajoli, Alessandra, MD ; Cardenas-Turanzas, Marylou, PhD ; Lerner, Susan, MS ; Jorgensen, Jeffrey L, MD ; Nogueras-González, Graciela M, MS ; Zacharian, Gracy, MS ; Huang, Xuelin, PhD ; Kantarjian, Hagop, Prof ; Garg, Naveen, MD ; Rosenwald, Andreas, Prof ; O'Brien, Susan, Prof</creatorcontrib><description>Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab in patients with high-risk CLL. Methods In this single-arm phase 2 study, we enrolled adult patients with high-risk CLL at the MD Anderson Cancer Center (Houston, TX, USA). All enrolled participants had high-risk cytogenetic abnormalities (deletion 17p, TP53 mutation, or deletion 11q) or a short progression-free survival (PFS <36 months) after previous first-line chemoimmunotherapy. Patients with symptomatic disease requiring therapy received 28-day cycles of once-daily ibrutinib 420 mg together with rituximab (375 mg/m2 , intravenously, every week during cycle 1, then once per cycle until cycle 6), followed by continuous daily single-agent ibrutinib 420 mg until disease progression or until toxicities or complications precluded further treatment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov number NCT01520519 , and is no longer accruing patients. Findings Between Feb 28, 2012, and Sept 11, 2012, we enrolled 40 patients with CLL with high-risk disease features, 20 of whom had deletion 17p (del[17p]) or TP53 mutations (16 previously treated, four untreated), 13 had relapsed CLL with deletion 11q (del[11q]), and seven a PFS less than 36 months after first-line chemoimmunotherapy. 18-month PFS in all patients was 78·0% (95% CI 60·6–88·5), whereas in those with a del(17p) or TP53 mutation it was 72·4% (45·6–87·6) Toxicity was mainly mild to moderate in severity (grade 1–2). Diarrhoea occurred in ten (25%) patients (grade 1 in nine patients and grade 2 in one), bleeding events in 14 (33%) patients (eight grade 1 and five grade 2), nausea or vomiting in 15 patients (38%) (ten grade 1 and five grade 2), and fatigue in seven (18%) patients (four grade 1 and three grade 2). Five patients (13%) had grade 3 infections (two lung infections, one upper respiratory tract infection, one sepsis, and one mucositis), and no grade 4 or 5 infections occurred. One patient had grade 4 neutropenia. Interpretation The encouraging safety and activity of ibrutinib and rituximab in this population of patients with high-risk CLL merits further investigation of this combination. Funding Pharmacyclics Inc, Cancer Prevention and Research Institute of Texas, Leukemia and Lymphoma Society, National Cancer Institute, MD Anderson Cancer Center.</description><identifier>ISSN: 1470-2045</identifier><identifier>EISSN: 1474-5488</identifier><identifier>DOI: 10.1016/S1470-2045(14)70335-3</identifier><identifier>PMID: 25150798</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Murine-Derived - adverse effects ; Antibodies, Monoclonal, Murine-Derived - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Cell adhesion & migration ; Constipation ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug therapy ; Female ; Hematology, Oncology and Palliative Medicine ; Humans ; Infections ; Insomnia ; Kaplan-Meier Estimate ; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell - mortality ; Male ; Maximum Tolerated Dose ; Medical prognosis ; Middle Aged ; Mutation ; Neoplasm Recurrence, Local - diagnosis ; Neoplasm Recurrence, Local - drug therapy ; Neoplasm Recurrence, Local - mortality ; Patient Selection ; Prognosis ; Pyrazoles - administration & dosage ; Pyrazoles - adverse effects ; Pyrimidines - administration & dosage ; Pyrimidines - adverse effects ; Quality of life ; Rituximab ; Survival Rate ; Treatment Outcome</subject><ispartof>The lancet oncology, 2014-09, Vol.15 (10), p.1090-1099</ispartof><rights>Elsevier Ltd</rights><rights>2014 Elsevier Ltd</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Sep 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c561t-d56c68f5e1c12d5ac2e6b4b3d35e8fd7a78dabca0b62696bc37ddb9f2730bd553</citedby><cites>FETCH-LOGICAL-c561t-d56c68f5e1c12d5ac2e6b4b3d35e8fd7a78dabca0b62696bc37ddb9f2730bd553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1558844618?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976,64364,64366,64368,72218</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25150798$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Burger, Jan A, Dr</creatorcontrib><creatorcontrib>Keating, Michael J, Prof</creatorcontrib><creatorcontrib>Wierda, William G, Prof</creatorcontrib><creatorcontrib>Hartmann, Elena, MD</creatorcontrib><creatorcontrib>Hoellenriegel, Julia, MS</creatorcontrib><creatorcontrib>Rosin, Nathalie Y, PhD</creatorcontrib><creatorcontrib>de Weerdt, Iris, MD</creatorcontrib><creatorcontrib>Jeyakumar, Ghayathri, MD</creatorcontrib><creatorcontrib>Ferrajoli, Alessandra, MD</creatorcontrib><creatorcontrib>Cardenas-Turanzas, Marylou, PhD</creatorcontrib><creatorcontrib>Lerner, Susan, MS</creatorcontrib><creatorcontrib>Jorgensen, Jeffrey L, MD</creatorcontrib><creatorcontrib>Nogueras-González, Graciela M, MS</creatorcontrib><creatorcontrib>Zacharian, Gracy, MS</creatorcontrib><creatorcontrib>Huang, Xuelin, PhD</creatorcontrib><creatorcontrib>Kantarjian, Hagop, Prof</creatorcontrib><creatorcontrib>Garg, Naveen, MD</creatorcontrib><creatorcontrib>Rosenwald, Andreas, Prof</creatorcontrib><creatorcontrib>O'Brien, Susan, Prof</creatorcontrib><title>Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study</title><title>The lancet oncology</title><addtitle>Lancet Oncol</addtitle><description>Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab in patients with high-risk CLL. Methods In this single-arm phase 2 study, we enrolled adult patients with high-risk CLL at the MD Anderson Cancer Center (Houston, TX, USA). All enrolled participants had high-risk cytogenetic abnormalities (deletion 17p, TP53 mutation, or deletion 11q) or a short progression-free survival (PFS <36 months) after previous first-line chemoimmunotherapy. Patients with symptomatic disease requiring therapy received 28-day cycles of once-daily ibrutinib 420 mg together with rituximab (375 mg/m2 , intravenously, every week during cycle 1, then once per cycle until cycle 6), followed by continuous daily single-agent ibrutinib 420 mg until disease progression or until toxicities or complications precluded further treatment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov number NCT01520519 , and is no longer accruing patients. Findings Between Feb 28, 2012, and Sept 11, 2012, we enrolled 40 patients with CLL with high-risk disease features, 20 of whom had deletion 17p (del[17p]) or TP53 mutations (16 previously treated, four untreated), 13 had relapsed CLL with deletion 11q (del[11q]), and seven a PFS less than 36 months after first-line chemoimmunotherapy. 18-month PFS in all patients was 78·0% (95% CI 60·6–88·5), whereas in those with a del(17p) or TP53 mutation it was 72·4% (45·6–87·6) Toxicity was mainly mild to moderate in severity (grade 1–2). Diarrhoea occurred in ten (25%) patients (grade 1 in nine patients and grade 2 in one), bleeding events in 14 (33%) patients (eight grade 1 and five grade 2), nausea or vomiting in 15 patients (38%) (ten grade 1 and five grade 2), and fatigue in seven (18%) patients (four grade 1 and three grade 2). Five patients (13%) had grade 3 infections (two lung infections, one upper respiratory tract infection, one sepsis, and one mucositis), and no grade 4 or 5 infections occurred. One patient had grade 4 neutropenia. Interpretation The encouraging safety and activity of ibrutinib and rituximab in this population of patients with high-risk CLL merits further investigation of this combination. Funding Pharmacyclics Inc, Cancer Prevention and Research Institute of Texas, Leukemia and Lymphoma Society, National Cancer Institute, MD Anderson Cancer Center.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antibodies, Monoclonal, Murine-Derived - adverse effects</subject><subject>Antibodies, Monoclonal, Murine-Derived - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Cell adhesion & migration</subject><subject>Constipation</subject><subject>Disease-Free Survival</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Administration Schedule</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Infections</subject><subject>Insomnia</subject><subject>Kaplan-Meier Estimate</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - mortality</subject><subject>Male</subject><subject>Maximum Tolerated Dose</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Recurrence, Local - diagnosis</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Patient Selection</subject><subject>Prognosis</subject><subject>Pyrazoles - administration & dosage</subject><subject>Pyrazoles - adverse effects</subject><subject>Pyrimidines - administration & dosage</subject><subject>Pyrimidines - adverse effects</subject><subject>Quality of life</subject><subject>Rituximab</subject><subject>Survival Rate</subject><subject>Treatment Outcome</subject><issn>1470-2045</issn><issn>1474-5488</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkctu1TAQhiMEoqXwCCBLbIpEwI4v8WEBQhU3qRKLwtryZdK4J7faTiEvwHPjnBSQumE1Y-ubf-z_L4qnBL8imIjXF4TVuKww46eEvagxpbyk94rjfM1KzqS8f-g35Kh4FOMVxqQmmD8sjipOOK538rj4daEbSAvSg0PaJn_j82FskDdhTn7wBk3dHFHwaf7pe21QMwY06eRhSBH98KlFrb9sy-DjHtk2jIO3qFv6qR3tktYe5r2G3us3SKPoh8sOSh36l2hqdQRUoZhmtzwuHjS6i_Dktp4U3z9--Hb2uTz_-unL2fvz0nJBUum4sEI2HIgllePaViAMM9RRDrJxta6l08ZqbEQldsJYWjtndk1VU2wc5_SkON10pzBezxCT6n200HV6gHGOinAhJMsG7zL6_A56Nc5hyK_LFJeSMUFkpvhG2TDGGKBRU8g-hUURrNag1CEotaagCFOHoBTNc89u1WfTg_s79SeZDLzbAMh23HgIKtpsugXnA9ik3Oj_u-LtHQXb5USt7vawQPz3GxUrhTeRVWOtWYHS34ABuVc</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Burger, Jan A, Dr</creator><creator>Keating, Michael J, Prof</creator><creator>Wierda, William G, Prof</creator><creator>Hartmann, Elena, MD</creator><creator>Hoellenriegel, Julia, MS</creator><creator>Rosin, Nathalie Y, PhD</creator><creator>de Weerdt, Iris, MD</creator><creator>Jeyakumar, Ghayathri, MD</creator><creator>Ferrajoli, Alessandra, MD</creator><creator>Cardenas-Turanzas, Marylou, PhD</creator><creator>Lerner, Susan, MS</creator><creator>Jorgensen, Jeffrey L, MD</creator><creator>Nogueras-González, Graciela M, MS</creator><creator>Zacharian, Gracy, MS</creator><creator>Huang, Xuelin, PhD</creator><creator>Kantarjian, Hagop, Prof</creator><creator>Garg, Naveen, MD</creator><creator>Rosenwald, Andreas, Prof</creator><creator>O'Brien, Susan, Prof</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TZ</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7T5</scope></search><sort><creationdate>20140901</creationdate><title>Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study</title><author>Burger, Jan A, Dr ; Keating, Michael J, Prof ; Wierda, William G, Prof ; Hartmann, Elena, MD ; Hoellenriegel, Julia, MS ; Rosin, Nathalie Y, PhD ; de Weerdt, Iris, MD ; Jeyakumar, Ghayathri, MD ; Ferrajoli, Alessandra, MD ; Cardenas-Turanzas, Marylou, PhD ; Lerner, Susan, MS ; Jorgensen, Jeffrey L, MD ; Nogueras-González, Graciela M, MS ; Zacharian, Gracy, MS ; Huang, Xuelin, PhD ; Kantarjian, Hagop, Prof ; Garg, Naveen, MD ; Rosenwald, Andreas, Prof ; O'Brien, Susan, Prof</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c561t-d56c68f5e1c12d5ac2e6b4b3d35e8fd7a78dabca0b62696bc37ddb9f2730bd553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Administration, Oral</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antibodies, Monoclonal - 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diagnosis</topic><topic>Neoplasm Recurrence, Local - drug therapy</topic><topic>Neoplasm Recurrence, Local - mortality</topic><topic>Patient Selection</topic><topic>Prognosis</topic><topic>Pyrazoles - administration & dosage</topic><topic>Pyrazoles - adverse effects</topic><topic>Pyrimidines - administration & dosage</topic><topic>Pyrimidines - adverse effects</topic><topic>Quality of life</topic><topic>Rituximab</topic><topic>Survival Rate</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Burger, Jan A, Dr</creatorcontrib><creatorcontrib>Keating, Michael J, Prof</creatorcontrib><creatorcontrib>Wierda, William G, Prof</creatorcontrib><creatorcontrib>Hartmann, Elena, MD</creatorcontrib><creatorcontrib>Hoellenriegel, Julia, MS</creatorcontrib><creatorcontrib>Rosin, Nathalie Y, PhD</creatorcontrib><creatorcontrib>de Weerdt, Iris, MD</creatorcontrib><creatorcontrib>Jeyakumar, Ghayathri, MD</creatorcontrib><creatorcontrib>Ferrajoli, Alessandra, MD</creatorcontrib><creatorcontrib>Cardenas-Turanzas, Marylou, PhD</creatorcontrib><creatorcontrib>Lerner, Susan, MS</creatorcontrib><creatorcontrib>Jorgensen, Jeffrey L, MD</creatorcontrib><creatorcontrib>Nogueras-González, Graciela M, MS</creatorcontrib><creatorcontrib>Zacharian, Gracy, MS</creatorcontrib><creatorcontrib>Huang, Xuelin, PhD</creatorcontrib><creatorcontrib>Kantarjian, Hagop, Prof</creatorcontrib><creatorcontrib>Garg, Naveen, MD</creatorcontrib><creatorcontrib>Rosenwald, Andreas, Prof</creatorcontrib><creatorcontrib>O'Brien, Susan, Prof</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Pharma and Biotech Premium PRO</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Lancet Titles</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Immunology Abstracts</collection><jtitle>The lancet oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burger, Jan A, Dr</au><au>Keating, Michael J, Prof</au><au>Wierda, William G, Prof</au><au>Hartmann, Elena, MD</au><au>Hoellenriegel, Julia, MS</au><au>Rosin, Nathalie Y, PhD</au><au>de Weerdt, Iris, MD</au><au>Jeyakumar, Ghayathri, MD</au><au>Ferrajoli, Alessandra, MD</au><au>Cardenas-Turanzas, Marylou, PhD</au><au>Lerner, Susan, MS</au><au>Jorgensen, Jeffrey L, MD</au><au>Nogueras-González, Graciela M, MS</au><au>Zacharian, Gracy, MS</au><au>Huang, Xuelin, PhD</au><au>Kantarjian, Hagop, Prof</au><au>Garg, Naveen, MD</au><au>Rosenwald, Andreas, Prof</au><au>O'Brien, Susan, Prof</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study</atitle><jtitle>The lancet oncology</jtitle><addtitle>Lancet Oncol</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>15</volume><issue>10</issue><spage>1090</spage><epage>1099</epage><pages>1090-1099</pages><issn>1470-2045</issn><eissn>1474-5488</eissn><coden>LANCAO</coden><abstract>Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL). We investigated the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab in patients with high-risk CLL. Methods In this single-arm phase 2 study, we enrolled adult patients with high-risk CLL at the MD Anderson Cancer Center (Houston, TX, USA). All enrolled participants had high-risk cytogenetic abnormalities (deletion 17p, TP53 mutation, or deletion 11q) or a short progression-free survival (PFS <36 months) after previous first-line chemoimmunotherapy. Patients with symptomatic disease requiring therapy received 28-day cycles of once-daily ibrutinib 420 mg together with rituximab (375 mg/m2 , intravenously, every week during cycle 1, then once per cycle until cycle 6), followed by continuous daily single-agent ibrutinib 420 mg until disease progression or until toxicities or complications precluded further treatment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov number NCT01520519 , and is no longer accruing patients. Findings Between Feb 28, 2012, and Sept 11, 2012, we enrolled 40 patients with CLL with high-risk disease features, 20 of whom had deletion 17p (del[17p]) or TP53 mutations (16 previously treated, four untreated), 13 had relapsed CLL with deletion 11q (del[11q]), and seven a PFS less than 36 months after first-line chemoimmunotherapy. 18-month PFS in all patients was 78·0% (95% CI 60·6–88·5), whereas in those with a del(17p) or TP53 mutation it was 72·4% (45·6–87·6) Toxicity was mainly mild to moderate in severity (grade 1–2). Diarrhoea occurred in ten (25%) patients (grade 1 in nine patients and grade 2 in one), bleeding events in 14 (33%) patients (eight grade 1 and five grade 2), nausea or vomiting in 15 patients (38%) (ten grade 1 and five grade 2), and fatigue in seven (18%) patients (four grade 1 and three grade 2). Five patients (13%) had grade 3 infections (two lung infections, one upper respiratory tract infection, one sepsis, and one mucositis), and no grade 4 or 5 infections occurred. One patient had grade 4 neutropenia. Interpretation The encouraging safety and activity of ibrutinib and rituximab in this population of patients with high-risk CLL merits further investigation of this combination. Funding Pharmacyclics Inc, Cancer Prevention and Research Institute of Texas, Leukemia and Lymphoma Society, National Cancer Institute, MD Anderson Cancer Center.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>25150798</pmid><doi>10.1016/S1470-2045(14)70335-3</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1470-2045 |
| ispartof | The lancet oncology, 2014-09, Vol.15 (10), p.1090-1099 |
| issn | 1470-2045 1474-5488 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1566841019 |
| source | MEDLINE; Elsevier ScienceDirect Journals; ProQuest Central UK/Ireland |
| subjects | Administration, Oral Adult Aged Aged, 80 and over Antibodies, Monoclonal - therapeutic use Antibodies, Monoclonal, Murine-Derived - adverse effects Antibodies, Monoclonal, Murine-Derived - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cell adhesion & migration Constipation Disease-Free Survival Dose-Response Relationship, Drug Drug Administration Schedule Drug therapy Female Hematology, Oncology and Palliative Medicine Humans Infections Insomnia Kaplan-Meier Estimate Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Leukemia, Lymphocytic, Chronic, B-Cell - mortality Male Maximum Tolerated Dose Medical prognosis Middle Aged Mutation Neoplasm Recurrence, Local - diagnosis Neoplasm Recurrence, Local - drug therapy Neoplasm Recurrence, Local - mortality Patient Selection Prognosis Pyrazoles - administration & dosage Pyrazoles - adverse effects Pyrimidines - administration & dosage Pyrimidines - adverse effects Quality of life Rituximab Survival Rate Treatment Outcome |
| title | Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T15%3A23%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Safety%20and%20activity%20of%20ibrutinib%20plus%20rituximab%20for%20patients%20with%20high-risk%20chronic%20lymphocytic%20leukaemia:%20a%20single-arm,%20phase%202%20study&rft.jtitle=The%20lancet%20oncology&rft.au=Burger,%20Jan%20A,%20Dr&rft.date=2014-09-01&rft.volume=15&rft.issue=10&rft.spage=1090&rft.epage=1099&rft.pages=1090-1099&rft.issn=1470-2045&rft.eissn=1474-5488&rft.coden=LANCAO&rft_id=info:doi/10.1016/S1470-2045(14)70335-3&rft_dat=%3Cproquest_cross%3E3419627681%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1558844618&rft_id=info:pmid/25150798&rft_els_id=S1470204514703353&rfr_iscdi=true |