{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:07:40Z","timestamp":1791050860831,"version":"4.1.0"},"reference-count":28,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2010,1,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Flavopiridol downmodulates antiapoptotic proteins associated with resistance to fludarabine and rituximab and is effective against p53-mutated chronic lymphocytic leukemia (CLL). We conducted a phase I study of flavopiridol, fludarabine, and rituximab (FFR) in patients with mantle-cell lymphoma (MCL), indolent B-cell non-Hodgkin's lymphomas (B-NHL), and CLL to determine the activity of FFR. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Therapy included fludarabine 25 mg\/m<jats:sup>2<\/jats:sup> intravenously (IV) days 1 to 5 and rituximab 375 mg\/m<jats:sup>2<\/jats:sup> day 1 every 28 days for 6 cycles. We administered flavopiridol 50 mg\/m<jats:sup>2<\/jats:sup> by 1-hour IV bolus (IVB) day 1 (n = 15); day 1 to 2 (n = 6); 20 mg\/m<jats:sup>2<\/jats:sup> 30-minute IVB + 20 mg\/m<jats:sup>2<\/jats:sup> 4-hour IV infusion (n = 3); or 30 mg\/m<jats:sup>2<\/jats:sup> + 30 mg\/m<jats:sup>2<\/jats:sup> (n = 14). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Thirty-eight patients (median age, 62 years) with MCL (n = 10); indolent B-NHL including follicular (n = 9), marginal zone (n = 4), lymphoplasmacytic (n = 1), or small lymphocytic lymphoma (n = 3); and CLL (n = 11), were enrolled. Twenty-two patients were previously untreated; 16 had received one to two prior therapies. Two patients in cohort 2 developed grade 3 dose-limiting toxicity (seizures, renal insufficiency). The median number of treatment cycles was 4, with cytopenias (n = 10) and fatigue (n = 3) the most common reasons for early discontinuation. Overall response rate was 82% (complete response, 50%; unconfirmed complete response, 5%; partial response, 26%), including 80% of patients with MCL (median age, 68; seven complete responses, one partial response). Median progression-free survival (PFS) was 25.6 months. Median PFS of patients with nonblastoid variant MCL (n = 8) was 35.9 months. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> FFR was active in MCL, indolent B-NHL, and CLL and should be studied for older patients with MCL who are not candidates for aggressive chemotherapy. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2009.24.1570","type":"journal-article","created":{"date-parts":[[2009,12,15]],"date-time":"2009-12-15T03:07:08Z","timestamp":1260846428000},"page":"418-423","source":"Crossref","is-referenced-by-count":78,"title":["Flavopiridol, Fludarabine, and Rituximab in Mantle Cell Lymphoma and Indolent B-Cell Lymphoproliferative Disorders"],"prefix":"10.1200","volume":"28","author":[{"given":"Thomas S.","family":"Lin","sequence":"first","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristie A.","family":"Blum","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane Beth","family":"Fischer","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"Ruppert","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Porcu","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H.","family":"Kraut","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Baiocchi","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mollie E.","family":"Moran","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry J.","family":"Schaaf","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Grever","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[{"name":"From the Division of Hematology and Oncology, The Ohio State University; Center for Biostatistics, The Ohio State University, Columbus, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13868-8"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/01.moh.0000138682.13354.da"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2004.09.001"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.1825"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.4.1262"},{"key":"B6","first-page":"37","volume":"27","author":"McLaughlin P","year":"2000","journal-title":"Semin Oncol"},{"key":"B7","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1182\/blood-2004-04-1323","volume":"104","author":"Forstpointer R","year":"2004","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2002.03959.x"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-04-1258"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.12.516"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.12.051"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.6.1580.bloodjournal8561580"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012283432602"},{"key":"B14","first-page":"2973","volume":"56","author":"Carlson BA","year":"1996","journal-title":"Cancer Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/84.22.1736"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06710.x"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.5.376"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(93)90590-S"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.2.393"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.10.3804"},{"key":"B20a","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.6944"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-168583"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-020735"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.4.1244"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.12.4990.bloodjournal87124990"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.09.057"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-095331"},{"key":"B27","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1182\/blood-2006-04-016725","volume":"108","author":"Forstpointner R","year":"2006","journal-title":"Blood"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2009.24.1570","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T23:46:39Z","timestamp":1653522399000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2009.24.1570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1,20]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2010,1,20]]}},"alternative-id":["10.1200\/JCO.2009.24.1570"],"URL":"https:\/\/doi.org\/10.1200\/jco.2009.24.1570","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,1,20]]}}}