Phase I dose escalation study of BI 836826 (CD37 antibody) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma

BI 836826 is a chimeric immunoglobulin G1 antibody targeting CD37, a tetraspanin transmembrane protein predominantly expressed on normal and malignant B cells. This phase I, open-label study used a modified 3 + 3 design to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, and preliminary activity of BI 836826 in patients with relapsed/refractory B cell non-Hodgkin lymphoma (NHL; NCT01403948). Eligible patients received up to three courses comprising an intravenous infusion (starting dose: 1 mg) once weekly for 4 weeks followed by an observation period of 27 (Course 1, 2) or 55 days (Course 3). Patients had to demonstrate clinical benefit before commencing treatment beyond course 2. Forty-eight patients were treated. In the dose escalation phase (1-200 mg) involving 37 Caucasian patients, the MTD was 100 mg. Dose-limiting toxicities occurred in four patients during the MTD evaluation period, and included stomatitis, febrile neutropenia, hypocalcemia, hypokalemia, and hypophosphatemia. The most common adverse events were neutropenia (57%), leukopenia (57%), and thrombocytopenia (41%), and were commonly of grade 3 or 4. Overall, 18 (38%) patients experienced infusion-related reactions, which were mostly grade 1 or 2. Preliminary evidence of anti-tumor activity was seen; three patients responded to treatment, including one complete remission in a Korean patient with diffuse large B cell lymphoma. BI 836826 plasma exposure increased more than proportionally with increasing doses. BI 836826 demonstrated preliminary activity; the most frequent adverse events were hematotoxicity and infusion-related reactions which were manageable after amending the infusion schedule. Although BI 856826 will not undergo further clinical development, these results confirm CD37 as a valid therapeutic target in B cell NHL

Variation of functional traits in trees from a biogeographically complex Mexican cloud forest

Background: We report 96- and 144-week follow-up data from VERxVE, demonstrating that nevirapine (NVP) extended release (XR) 400 mg once daily was non-inferior to NVP immediate release (IR) 200 mg twice daily, each administered on a backbone of emtricitabine/tenofovir. Methods: VERxVE was a double-blind, double-dummy, non-inferiority study in adults with screening viral load (VL) >1000 copies/mL and CD4+ cell count <400 cells/mm3 (males) or <250 cells/mm3 (females). Randomisation was stratified by baseline VL (copies/mL) ? 100,000 or >100,000. The primary endpoint was confirmed virologic response (<50 copies/mL) at week 48. Cochran's statistic incorporating baseline VL strata tested non-inferiority of XR efficacy versus IR. Secondary endpoints included 144-week sustained virologic response and safety. Results: In all, 1011 patients were randomised and treated with NVP: 736 (XR n=378; IR n= 358) completed 144 weeks. Virologic response was 63.6% for NVP XR and 58.5% for NVP IR (adjusted difference of 4.8% [95% confidence interval -1.1% to 10.8%] favouring NVP XR). No significant differences were seen in changes in CD4+ T-cell counts from baseline, virologic failures or total discontinuation rates between treatment arms, regardless of demographic or baseline characteristics. Conclusions: NVP XR demonstrated non-inferior virologic efficacy to NVP IR in treatment-naive HIV-infected patients and was well tolerated out to week 144, with a safety profile similar to NVP IR. " 2013 Brinson C, et al.",,,,,,"10.4172/2155-6113.1000233",,,"http://hdl.handle.net/20.500.12104/45675","http://www.scopus.com/inward/record.url?eid=2-s2.0-84884951885&partnerID=40&md5=6b5a7deacf969fec1b71911841c1011f",,,,,,"8",,"Journal of AIDS and Clinical Research",,,,"4",,"Scopus",,,,,,"Clinical trial; Extended-release formulation; Hiv; Nevirapine; Once-daily dosing",,,,,,"Verxve 144-week results: Nevirapine extended release (nvp xr) qd versus nvp immediate release (ir) bid with ftc/tdf in treatment-naive hiv-1 patients",,"Article" "47427","123456789/35008",,"Saldaña-Acosta, A., Departamento de Ecología y Recursos Naturales, Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM), México, 04510 D.F., Mexico, Instituto Manantlán de Ecología y Biodiversidad, CUCSUR, Universidad de Guadalajara, Autlán de Navarro, 48900 Jalisco, Mexico; Meave, J.A., Departamento de Ecología y Recursos Naturales, Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM), México, 04510 D.F., Mexico; Paz, H., Centro de Investigaciones en Ecosistemas, UNAM, Morelia, 58190 Michoacán, Mexico; Sánchez-Velásquez, L.R., Instituto de Biotecnología y Ecología Aplicada, Dirección General de Investigaciones, Universidad Veracruzana, Xalapa, Veracruz, Mexico; Villaseñor, J.L., Departamento de Botánica, Instituto de Biología, UNAM, México, 04510 D.F., Mexico; Martínez-Ramos, M., Centro de Investigaciones en Ecosistemas, UNAM, Morelia, 58190 Michoacán, Mexico",,"Saldana-Acosta, A

Verxve 144-week results: Nevirapine extended release (nvp xr) qd versus nvp immediate release (ir) bid with ftc/tdf in treatment-naive hiv-1 patients

Background: We report 96- and 144-week follow-up data from VERxVE, demonstrating that nevirapine (NVP) extended release (XR) 400 mg once daily was non-inferior to NVP immediate release (IR) 200 mg twice daily, each administered on a backbone of emtricitabine/tenofovir. Methods: VERxVE was a double-blind, double-dummy, non-inferiority study in adults with screening viral load (VL) >1000 copies/mL and CD4+ cell count <400 cells/mm3 (males) or <250 cells/mm3 (females). Randomisation was stratified by baseline VL (copies/mL) ≤ 100,000 or >100,000. The primary endpoint was confirmed virologic response (<50 copies/mL) at week 48. Cochran's statistic incorporating baseline VL strata tested non-inferiority of XR efficacy versus IR. Secondary endpoints included 144-week sustained virologic response and safety. Results: In all, 1011 patients were randomised and treated with NVP: 736 (XR n=378; IR n= 358) completed 144 weeks. Virologic response was 63.6% for NVP XR and 58.5% for NVP IR (adjusted difference of 4.8% [95% confidence interval -1.1% to 10.8%] favouring NVP XR). No significant differences were seen in changes in CD4+ T-cell counts from baseline, virologic failures or total discontinuation rates between treatment arms, regardless of demographic or baseline characteristics. Conclusions: NVP XR demonstrated non-inferior virologic efficacy to NVP IR in treatment-naïve HIV-infected patients and was well tolerated out to week 144, with a safety profile similar to NVP IR. © 2013 Brinson C, et al