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Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia
| Content Provider | Scilit |
|---|---|
| Author | Flinn, Ian W. Gribben, John G. Dyer, Martin J. S. Wierda, William Maris, Michael B. Furman, Richard R. Hillmen, Peter Rogers, Kerry A. Iyer, Swaminathan Padmanabhan Quillet-Mary, Anne Ysebaert, Loic Walter, Henrik Verdugo, Maria Klein, Christian Huang, Huang Jiang, Yanwen Lozanski, Gerard Pignataro, Daniela Soriano Humphrey, Kathryn Mobasher, Mehrdad Kipps, Thomas J. |
| Copyright Year | 2019 |
| Description | This single-arm, open-label, phase 1b study evaluated the maximum tolerated dose (MTD) of venetoclax when given with obinutuzumab and its safety and tolerability in patients with relapsed/refractory (R/R) or previously untreated (first line [1L]) chronic lymphocytic leukemia (CLL). Venetoclax dose initially was escalated (100-400 mg) in a 3 + 3 design to define MTD combined with standard-dose obinutuzumab. Patients received venetoclax (schedule A) or obinutuzumab (schedule B) first to compare safety and determine dose/schedule for expansion. Venetoclax-obinutuzumab was administered for 6 cycles, followed by venetoclax monotherapy until disease progression (R/R) or fixed duration 1-year treatment (1L). Fifty R/R and 32 1L patients were enrolled. No dose-limiting toxicities were observed. Safety, including incidence of tumor lysis syndrome (TLS), did not differ between schedules (2 laboratory TLSs per schedule). Schedule B and a 400-mg dose of venetoclax were chosen for expansion. The most common grade 3-4 adverse event was neutropenia (R/R, 58% of patients; 1L, 53%). Rates of grade 3-4 infections were 29% (R/R) and 13% (1L); no fatal infections occurred in 1L. All infusion-related reactions were grade 1-2, except for 2 grade 3 events. No clinical TLS was observed. Overall best response rate was 95% in R/R (complete response [CR]/CR with incomplete marrow recovery [CRi], 37%) and 100% in 1L (CR/CRi, 78%) patients. Rate of undetectable (<10−4) minimal residual disease (uMRD) in peripheral blood for R/R and 1L patients, respectively, was 64% and 91% ≥3 months after last obinutuzumab dose. Venetoclax and obinutuzumab therapy had an acceptable safety profile and elicited durable responses and high rates of uMRD. This trial was registered at www.clinicaltrials.gov as #NCT01685892. |
| Related Links | https://leicester.figshare.com/articles/Phase_1b_study_of_venetoclax-obinutuzumab_in_previously_untreated_and_relapsed_refractory_chronic_lymphocytic_leukemia_/10238636/files/18478529.pdf |
| Ending Page | 2775 |
| Page Count | 11 |
| Starting Page | 2765 |
| DOI | 10.1182/blood-2019-01-896290 |
| Journal | Blood |
| Issue Number | 26 |
| Volume Number | 133 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2019-06-27 |
| Access Restriction | Open |
| Subject Keyword | Hematology Safety Treatment Grade Schedule Tolerated R/r Venetoclax Obinutuzumab Journal: Blood (Vol- 2019, Issue- 26) |
| Content Type | Text |
| Resource Type | Article |
