دورية أكاديمية
Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial
| العنوان: | Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial |
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| المؤلفون: | Lonial, Sagar, Weiss, Brendan M, Usmani, Saad Z, Singhal, Seema, Chari, Ajai, Bahlis, Nizar J, Belch, Andrew, Krishnan, Amrita, Vescio, Robert A, Mateos, Maria Victoria, Mazumder, Amitabha, Orlowski, Robert Z, Sutherland, Heather J, Bladé, Joan, Scott, Emma C, Oriol, Albert, Berdeja, Jesus, Gharibo, Mecide, Stevens, Don A, Leblanc, Richard, Sebag, Michael, Callander, Natalie, Jakubowiak, Andrzej, White, Darrell, De La Rubia, Javier, Richardson, Paul G., Lisby, Steen, Feng, Huaibao, Uhlar, Clarissa M, Khan, Imran, Ahmadi, Tahamtan, Voorhees, Peter M |
| المصدر: | The Lancet, 387(10027) |
| سنة النشر: | 2016 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Kaplan-Meier Estimate, Male, Antineoplastic Agents, Antibodies, Monoclonal, Spain, Middle Aged, Disease-Free Survival, United States, Antineoplastic Combined Chemotherapy Protocols, daratumumab, Female, Drug Administration Schedule, Aged, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local, Multiple Myeloma, Canada, Treatment Outcome, Humans, Adult |
| الوصف: | BACKGROUND: New treatment options are needed for patients with multiple myeloma that is refractory to proteasome inhibitors and immunomodulatory drugs. We assessed daratumumab, a novel CD38-targeted monoclonal antibody, in patients with refractory multiple myeloma. METHODS: In this open-label, multicentre, phase 2 trial done in Canada, Spain, and the USA, patients (age ≥18 years) with multiple myeloma who were previously treated with at least three lines of therapy (including proteasome inhibitors and immunomodulatory drugs), or were refractory to both proteasome inhibitors and immunomodulatory drugs, were randomly allocated in a 1:1 ratio to receive intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 stage 1 of the study, to decide the dose for further assessment in part 2. Patients received 8 mg/kg every 4 weeks, or 16 mg/kg per week for 8 weeks (cycles 1 and 2), then every 2 weeks for 16 weeks (cycles 3-6), and then every 4 weeks thereafter (cycle 7 and higher). The allocation schedule was computer-generated and randomisation, with permuted blocks, was done centrally with an interactive web response system. In part 1 stage 2 and part 2, patients received 16 mg/kg dosed as in part 1 stage 1. The primary endpoint was overall response rate (partial response [PR] + very good PR + complete response [CR] + stringent CR). All patients who received at least one dose of daratumumab were included in the analysis. The trial is registered with ClinicalTrials.gov, number NCT01985126. FINDINGS: The study is ongoing. In part 1 stage 1 of the study, 18 patients were randomly allocated to the 8 mg/kg group and 16 to the 16 mg/kg group. Findings are reported for the 106 patients who received daratumumab 16 mg/kg in parts 1 and 2. Patients received a median of five previous lines of therapy (range 2-14). 85 (80%) patients had previously received autologous stem cell transplantation, 101 (95%) were refractory to the most recent proteasome inhibitors and immunomodulatory drugs used, and 103 (97%) were refractory to the last ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/c9e2-m654Test; https://cdr.lib.unc.edu/downloads/xs55mj293?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/xs55mj293Test |
| DOI: | 10.17615/c9e2-m654 |
| الإتاحة: | https://doi.org/10.17615/c9e2-m654Test https://cdr.lib.unc.edu/downloads/xs55mj293?file=thumbnailTest https://cdr.lib.unc.edu/downloads/xs55mj293Test |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.C4BAED82 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/c9e2-m654 |
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