共查询到20条相似文献,搜索用时 15 毫秒
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Jesus G. Berdeja Lowell L. Hart Joseph R. Mace Edward R. Arrowsmith James H. Essell Rami S. Owera John D. Hainsworth Ian W. Flinn 《Haematologica》2015,100(5):670-676
The purpose of this study was to assess the safety and efficacy of the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma. Patients with multiple myeloma who had relapsed after at least one prior treatment were eligible to participate. In the dose escalation part of the study a standard 3+3 design was used to determine the maximum tolerated dose of four planned dose levels of the combination of carfilzomib and panobinostat. Panobinostat was administered on days 1, 3, 5, 15, 17, and 19. Carfilzomib was administered on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Treatment was continued until progression or intolerable toxicity. Forty-four patients were accrued into the trial, 13 in the phase I part and 31 in the phase II part of the study. The median age of the patients was 66 years and the median number of prior therapies was five. The expansion dose was established as 30 mg panobinostat, 20/45 mg/m2 carfilzomib. The overall response rate was 67% for all patients, 67% for patients refractory to prior proteasome inhibitor treatment and 75% for patients refractory to prior immune modulating drug treatment. At a median follow up of 17 months, median progression-free survival was 7.7 months, median time to progression was 7.7 months, and median overall survival had not been reached. The regimen was well tolerated, although there were several panobinostat dose reductions. In conclusion, the combination of panobinostat and carfilzomib is feasible and effective in patients with relapsed/refractory multiple myeloma. (Trial registered at ClinicalTrials.gov: ) NCT01496118相似文献
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Phase II and pharmacokinetic study of thalidomide in Japanese patients with relapsed/refractory multiple myeloma 总被引:1,自引:0,他引:1
Hirokazu Murakami Kazuyuki Shimizu Morio Sawamura Kenshi Suzuki Isamu Sugiura Hiroshi Kosugi Chihiro Shimazaki Masafumi Taniwaki Masahiro Abe Toshiyuki Takagi 《International journal of hematology》2009,89(5):636-641
To obtain approval from the Ministry of Health, Labor and Welfare of Japan, a phase II study was conducted to assess the pharmacokinetics
and pharmacodynamics of thalidomide along with its efficacy and safety in Japanese patients with multiple myeloma. Between
2005 and 2006, 42 patients were enrolled, and 37 patients met eligibility criteria. Of the 37 patients, 3 were excluded from
efficacy analysis because of short duration of thalidomide administration (<4 weeks). The overall response rate was 35.3%
(12/34), including partial response of 14.7% (5/34) and minimal response of 20.6% (7/34). The adverse events observed in high
frequency (>40%) were leukopenia, neutropenia, drowsiness, dry mouth, and constipation. Grade 3 neutropenia was observed in
nine cases. Peripheral neuropathy and eruption were observed in about one-quarter of the patients. Deep vein thrombosis was
not observed. At a single oral dose of thalidomide (100 mg), the C
max was 1.68 ± 0.41 μg/ml, T
max was 4.54 ± 1.71 h, T
1/2 was 4.86 ± 0.44 h, and AUC was 15.87 ± 3.05 μg h/ml. Low-dose thalidomide was an effective and tolerable treatment for Japanese
patients with relapsed/refractory myeloma. Leukopenia and neutropenia were the most serious adverse events. The pharmacokinetics
was similar to those observed in Caucasian patients. 相似文献
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Phase I study of carfilzomib,lenalidomide, vorinostat,and dexamethasone in patients with relapsed and/or refractory multiple myeloma 下载免费PDF全文
David H. Vesole Elizabeth Bilotti Joshua R. Richter Ann McNeill Laura McBride Laura Raucci Palka Anand Urszula Bednarz Kristin Ivanovski Judith Smith Veena Batra Adolfo Aleman Taliah Sims Laura Guerrero Anthony Mato David S. Siegel 《British journal of haematology》2015,171(1):52-59
Research has shown that proteasome inhibitors (e.g., carfilzomib), immunomodulatory agents (e.g., lenalidomide), histone deacetylase inhibitors (e.g., vorinostat) and corticosteroids (e.g., dexamethasone) have synergistic anti‐multiple myeloma (MM) activity. This phase I dose‐escalation study evaluated a regimen combining carfilzomib, lenalidomide, vorinostat and dexamethasone (QUAD) in patients with relapsed and/or refractory MM. Seventeen patients received carfilzomib (15, 20, or 20/27 mg/m2; 30‐min infusion; days 1, 2, 8, 9, 15, 16), lenalidomide (15 or 25 mg; days 1–21), vorinostat (300 or 400 mg; days 1–7, 15–21), and dexamethasone (40 mg; days 1, 8, 15, 22) in 28‐d cycles. No dose‐limiting toxicities were observed; the maximum tolerated dose was not reached. The maximum administered dose was carfilzomib 20/27 mg/m2, lenalidomide 25 mg, vorinostat 400 mg, and dexamethasone 40 mg. Common grade ≥3 adverse events included neutropenia (53%), thrombocytopenia (53%) and anaemia (41%). The overall response rate was 53%: 12% of patients achieved a very good partial response (PR) and 41% of patients achieved a PR. At a median follow‐up of 10 months, median progression‐free survival was 12 months and median overall survival was not reached. Treatment with QUAD was feasible and had encouraging activity in patients with relapsed and/or refractory MM. 相似文献
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Wu KL Beksac M van Droogenbroeck J Amadori S Zweegman S Sonneveld P 《Haematologica》2006,91(12):1722-1723
Arsenic trioxide induces growth inhibition and apoptosis in multiple myeloma cell lines. Reducing glutathione by ascorbic acid may enhance the efficacy of arsenic trioxide. Here we report the results of an international multi-center study of arsenic trioxide in combination with ascorbic acid and dexamethasone as treatment for patients with advanced multiple myeloma. 相似文献
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《British journal of haematology》2018,180(1):60-70
Immunomodulatory drugs including thalidomide, lenalidomide (LEN) and pomalidomide (POM), are effective for treating multiple myeloma (MM). POM has shown enhanced efficacy with dexamethasone (DEX). Pegylated liposomal doxorubicin (PLD) with bortezomib is US Food and Drug Administration‐approved for treating MM. PLD with LEN or thalidomide has shown efficacy for MM patients. LEN with DEX, PLD and bortezomib achieves high response rates. We evaluated the combination of POM with DEX 40 mg and PLD 5 mg/m2 with the latter two drugs administered on days 1, 4, 8 and 11 on a 28‐day cycle for the treatment of relapsed/refractory MM patients. During Phase 1, the maximum tolerated dose of POM was 4 mg, and was used in Phase 2, which also required patients to be refractory to LEN. However, neutropenia ≥ grade 3 was observed in 10/17 (59%) patients, and the dose was lowered to 3 mg. Median PFS was 5·4 months (range, 0·3–29·0 + months). Overall response rates for patients in Phase 2 were 39% and 31% among subjects receiving POM at 3 mg and 4 mg, respectively, and clinical benefit rates were 51% and 44%, respectively. POM, PLD and DEX is a treatment option for relapsed/refractory MM patients including those who are refractory to LEN. 相似文献
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Phase I/II study of weekly PM00104 (Zalypsis®) in patients with relapsed/refractory multiple myeloma 下载免费PDF全文
Enrique M. Ocio Albert Oriol Joan Bladé Ana I. Teruel Jesus Martín Javier de la Rubia Norma C. Gutiérrez José Rodríguez Díaz‐Pavón Sara Martínez González Cinthya Coronado Eva M. Fernández‐García Mariano Siguero Gómez Carlos Fernández‐Teruel Jesus San Miguel 《British journal of haematology》2016,172(4):625-628
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Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low‐dose dexamethasone: A pooled analysis 下载免费PDF全文
Philippe Moreau Meletios A. Dimopoulos Paul G. Richardson David S. Siegel Michele Cavo Paolo Corradini Katja Weisel Michel Delforge Peter O'Gorman Kevin Song Christine Chen Nizar Bahlis Albert Oriol Markus Hansson Martin Kaiser Pekka Anttila Reinier Raymakers Cristina Joao Gordon Cook Lars Sternas Tsvetan Biyukov Ana Slaughter Kevin Hong Jennifer Herring Xin Yu Mohamed Zaki Jesus San‐Miguel 《European journal of haematology》2017,99(3):199-206
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Jakubowiak AJ Richardson PG Zimmerman T Alsina M Kaufman JL Kandarpa M Kraftson S Ross CW Harvey C Hideshima T Sportelli P Poradosu E Gardner L Giusti K Anderson KC 《British journal of haematology》2012,158(4):472-480
The combination of lenalidomide-dexamethasone is active in multiple myeloma (MM). Preclinical data showed that the Akt inhibitor, perifosine, sensitized MM cells to lenalidomide and dexamethasone, providing the rationale for this Phase I, multicentre, single-arm study to assess the safety and determine the maximum-tolerated dose (MTD) of perifosine-lenalidomide-dexamethasone in relapsed and relapsed/refractory MM. Patients received escalating doses of perifosine 50-100 mg daily and lenalidomide 15-25 mg once daily on days 1-21 of each 28-d cycle, plus dexamethasone 20-40 mg weekly thereafter, as indicated. Thirty-two patients were enrolled across four dose cohorts. MTD was not reached, with 31 patients evaluable for safety/tolerability. The most common all-causality grade 1-2 adverse events were fatigue (48%) and diarrhoea (45%), and grade 3-4 neutropenia (26%), hypophosphataemia (23%), thrombocytopenia (16%), and leucopenia (13%). Among 30 evaluable patients, 73% (95% confidence interval, 57·5-89·2%) achieved a minimal response or better, including 50% with a partial response or better. Median progression-free survival was 10·8 months and median overall survival 30·6 months. Response was associated with phospho-Akt in pharmacodynamic studies. Perifosine-lenalidomide-dexamethasone was well tolerated and demonstrated encouraging clinical activity in relapsed and relapsed/refractory MM. 相似文献
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Shinsuke Iida Takaaki Chou Shinichiro Okamoto Hirokazu Nagai Kiyohiko Hatake Hirokazu Murakami Toshiyuki Takagi Kazuyuki Shimizu Henry Lau Kenichi Takeshita Masaaki Takatoku Tomomitsu Hotta 《International journal of hematology》2010,92(1):118-126
We conducted a multicenter, open-label study to investigate the safety, efficacy, and pharmacokinetics of lenalidomide in Japanese patients with relapsed or refractory multiple myeloma The study was composed of the “monotherapy phase”, a dose-escalation phase, to determine the tolerability to single agent lenalidomide and the “combination phase” to determine the safety and obtain preliminary data on the efficacy of lenalidomide plus dexamethasone. The primary end points were the tolerability to 25 mg lenalidomide and safety. Nine and six patients were enrolled in the monotherapy phase and the combination phase, respectively. Since 25 mg of monotherapy treatment did not satisfy the DLT criteria, this dose was employed in the combination phase. The major adverse event was myelosuppression. At the planned interim analysis (median study duration, 26.3 weeks), grade 3 or grade 4 neutropenia was observed with high frequency (66.7%). However, all adverse events observed were clinically manageable. In the combination cohort, the overall response rate (≥PR) was 100%. The pharmacokinetics of lenalidomide showed rapid absorption and elimination after both single and multiple doses. In conclusion, 25 mg of lenalidomide was given safely as a single agent or in combination with dexamethasone in Japanese patients. The good efficacy of the combination therapy was also demonstrated in this study. 相似文献
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Haruhito Totani Masaki Ri Chie Kato Takahiro Nakashima Nana Suzuki Shinya Hagiwara Takashi Kanamori Satsuki Murakami Arisa Masuda Shiori Kinoshita Takashi Yoshida Tomoko Narita Asahi Ito Shigeru Kusumoto Takashi Ishida Hirokazu Komatsu Shinsuke Iida 《International journal of hematology》2016,103(3):316-321
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Shaji K. Kumar Norbert Grzasko Sosana Delimpasi Wieslaw W. Jedrzejczak Sebastian Grosicki Marie-Christine Kyrtsonis Andrew Spencer Neeraj Gupta Zhaoyang Teng Catriona Byrne Richard Labotka Meletios A. Dimopoulos 《British journal of haematology》2019,184(4):536-546
There is a need for efficacious, convenient treatments with long-term tolerability for patients with relapsed/refractory multiple myeloma (RRMM). This phase 2 study evaluated the all-oral combination of ixazomib, cyclophosphamide and dexamethasone (ICd). Patients with RRMM received ixazomib 4 mg and cyclophosphamide 300 mg/m2 on days 1, 8 and 15, and dexamethasone 40 mg on days 1, 8, 15 and 22 in 28-day cycles. The primary endpoint was overall response rate (ORR). Seventy-eight patients were enrolled (median age 63·5 years). At data cut-off, patients had received a median of 12 treatment cycles; 31% remained on treatment. ORR was 48% [16% very good partial response or better (≥VGPR)]. ORR was 64% and 32% in patients aged ≥65 and <65 years (25% and 16% ≥VGPR), respectively. At a median follow-up of 15·2 months, median progression-free survival (PFS) was 14·2 months, with a trend towards better PFS in patients aged ≥65 years vs. <65 years (median 18·7 months vs. 12·0 months; hazard ratio 0·62, P = 0·14). ICd was well tolerated. The most common treatment-emergent adverse events were diarrhoea (33%), nausea (24%), upper respiratory tract infection (24%), and thrombocytopenia (22%); 10 patients (13%) had peripheral neuropathy (one grade 3). This study is registered at ClinicalTrials.gov (NCT02046070). 相似文献
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Andrzej J. Jakubowiak Jagoda K. Jasielec Cara A. Rosenbaum Craig E. Cole Ajai Chari Joseph Mikhael Jennifer Nam Amanda McIver Erica Severson Leonor A. Stephens Kathryn Tinari Shaun Rosebeck Todd M. Zimmerman Tyler Hycner Agata Turowski Theodore Karrison Jeffrey A. Zonder 《British journal of haematology》2019,186(4):549-560
Selinexor, an oral Selective Inhibitor of Nuclear Export, targets Exportin 1 (XPO1, also termed CRM1). Non-clinical studies support combining selinexor with proteasome inhibitors (PIs) and corticosteroids to overcome resistance in relapsed/refractory multiple myeloma (RRMM). We conducted a phase I dose-escalation trial of twice-weekly selinexor in combination with carfilzomib and dexamethasone (SKd) to determine maximum tolerated dose in patients with RRMM (N = 21), with an expansion cohort to assess activity in carfilzomib-refractory disease and identify a recommended phase II dose (RP2D). During dose escalation, there was one dose-limiting toxicity (cardiac failure). The RP2D of twice-weekly SKd was selinexor 60 mg, carfilzomib 20/27 mg/m2 and dexamethasone 20 mg. The most common grade 3/4 treatment-emergent adverse events included thrombocytopenia (71%), anaemia (33%), lymphopenia (33%), neutropenia (33%) and infections (24%). Rates of ≥minimal response, ≥partial response and very good partial response were 71%, 48% and 14%, respectively; similar response outcomes were observed for dual-class refractory (PI and immunomodulatory drug)/quad-exposed (carfilzomib, bortezomib, lenalidomide and pomalidomide) patients (n = 17), and patients refractory to carfilzomib in last line of therapy (n = 13). Median progression-free survival was 3·7 months, and overall survival was 22·4 months in the overall population. SKd was tolerable and re-established disease control in RRMM patients, including carfilzomib-refractory patients. Registered at ClinicalTrials.gov (NCT02199665) 相似文献
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Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma 总被引:15,自引:0,他引:15
Hussein MA Saleh M Ravandi F Mason J Rifkin RM Ellison R 《British journal of haematology》2004,125(4):470-476
Despite aggressive and innovative therapy, patients with multiple myeloma (MM) invariably relapse and die of their disease. New options for non-cytotoxic salvage therapy and additional therapeutic strategies are needed. Arsenic trioxide, an antitumour agent with a multifaceted mechanism of action, induces apoptosis in vitro in MM cell lines and freshly isolated cells from MM patients and, in preliminary studies, displayed clinical activity in patients with late-stage MM. A phase 2, multicentre, open-label study of arsenic trioxide was conducted in 24 MM patients; eight had relapsed and 16 were refractory to prior therapy. Patients received arsenic trioxide 0.25 mg/kg/d for 5 d/week during the first 2 weeks of each 4-week cycle. Sixteen patients had grade 3 or 4 neutropenia and one required antibiotics. Reductions (25% or more) in serum M-protein levels occurred in eight of 24 (33%) patients. An additional six (25%) patients had stable disease. The median time to response was 67.5 d, with a median duration of response of 130 d. Arsenic trioxide therapy lowered serum creatinine levels in two patients with high baseline values. These data indicate that arsenic trioxide is active and reasonably well tolerated as a single-agent salvage therapy, even in patients with late-stage, relapsed and refractory MM. 相似文献
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