Organization agility in Sri Lankan software industry

Agile Project management (APM) and Agile Software Development (ASD) are two widely discussed topics in the software industry. Since the inception of Agile Manifesto in 2001, many organizations have implemented agile methods with many more planning agile transitions. One of the core aspects of APM is adding value to the customer, which in turn provides high percentage of Return on Investment (ROI) to the organization. Consequently, Sri Lankan software industry needs to be much more agile with comparison to other countries to compete in the ever so challenging global software industry. The first objective of this research was to identify the agile implementation success factors in which influence the organizations to be agile. Second objective was to determine the level of implementation of agile success factors in the Sri Lankan software organizations, finally determine the organizational agility of the Sri Lankan software industry by analyzing the level of implementation of the identified success factors in organization. Research does not consider whether an organization has implemented a specific agile methodology but consider general traits or practices that are "agile." Research was carried out by considering 9 main agile implementation success factors: Customer satisfaction, customer collaboration, customer commitment, decision time, corporate culture, control, personal characteristics, social culture, and training and learning. These factors are categorized in to two broad categories: Organizational factors and people factors. Overall research findings evidenced that organizational agility in Sri Lankan software industry is "Highly agile" with respect to organizational factors with more than 60% of average responses, and "Very highly agile" with respect to people factors with more than 80% of average responses

Efficacy, Safety and Pharmacokinetic Results of a Phase III, Open-Label, Multicenter Study with a Plasma-Derived Von Willebrand Factor (VWF)/Factor VIII (FVIII) Concentrate in Pediatric Patients <12 Years of Age with Hemophilia A (SWIFTLY-HA Study)

Claudia Djambas Khayat,1 Genadi Iosava,2 Irina Romashevskaya,3 Oleksandra Stasyshyn,4 Marta Julia Lopez,5 Maria Teresa Pompa,6 Tobias Rogosch,7 Wilfried Seifert7 1Hospital Hôtel Dieu de France, Saint Joseph University, Beirut, Lebanon; 2Joint Stock Hematology and Transfusiology Research Institute, Tbilisi, Georgia; 3Republican Research Centre of Radiation Medicine and Human Ecology, Gomel, Belarus; 4Institute of Blood Pathology and Transfusion Medicine, Lviv, Ukraine; 5Guatemala City Hospital Roosevelt, Guatemala, Guatemala; 6Monterrey Nuevo Leon OCA Hospital (MIRC), Monterrey Nuevo Leon, Mexico; 7CSL Behring, Clinical Research and Development, Marburg, GermanyCorrespondence: Claudia Djambas KhayatHospital Hôtel Dieu de France, Saint Joseph University, Beirut, LebanonTel +9611613027Email [email protected]: Plasma-derived von Willebrand factor/factor VIII (pdVWF/FVIII; VONCENTO®, CSL Behring) is a high-concentration, low-volume, high-purity concentrate, with a high level of VWF high-molecular-weight multimers and a VWF/FVIII ratio of ∼ 2.4:1.Methods: This study (NCT01229007) investigated the pharmacokinetics (PK), efficacy and safety of pdVWF/FVIII in 35 previously treated (minimum 20 exposure days [EDs]) pediatric patients (< 12 years) with severe hemophilia A. PK was evaluated with a single 50 IU FVIII/kg dose of pdVWF/FVIII. Efficacy and safety analyses were performed during on-demand treatment (n=17) or prophylaxis (n=18) for up to 100 EDs with a maximum study duration of 12 months.Results: PK profiles were similar for patients aged < 6 years and those aged 6– 12 years, and, as expected, the youngest patients had an increased clearance. On-demand patients reported 320 non-surgical bleeding (NSB) events and received a median number of 29.0 infusions (median dose 34.2 IU FVIII/kg). Hemostatic efficacy was assessed by the investigator as excellent/good in all cases (24%/76%). The 18 patients in the prophylaxis arm experienced 173 NSB events (97 NSBs [56%] in three patients). Five patients (28%) had no NSB events. Overall, patients received a median number of 92 infusions (median dose 30.6 IU FVIII/kg). The majority of bleeds (92%) were successfully controlled with only one infusion. Hemostatic efficacy was assessed by the investigator as excellent (86%) or good (14%). Inhibitors occurred in three patients of which two were transient (low titer) and one persisted (high titer). These three patients had known risk factors for inhibitor development.Conclusion: This study demonstrated comparable PK profiles for pediatric patients aged < 6 years and aged 6– 12 years, and an excellent efficacy and safety profile in this population. The adverse events reported were mostly mild to moderate with inhibitor rates within the expected incidence range.Keywords: hemophilia A, von Willebrand factor, factor VIII, on-demand therapy, prophylaxis, hemostatic efficac

Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A : results of a multicenter clinical trial

Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. Summary: Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children <12 years of age with severe hemophilia A

Continuous lenalidomide treatment for newly diagnosed multiple myeloma.

BACKGROUND: Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednisone (MP) followed by placebo in patients 65 years of age or older with newly diagnosed multiple myeloma. METHODS: We randomly assigned patients who were ineligible for transplantation to receive MPR-R (nine 4-week cycles of MPR followed by lenalidomide maintenance therapy until a relapse or disease progression occurred [152 patients]) or to receive MPR (153 patients) or MP (154 patients) without maintenance therapy. The primary end point was progression-free survival. RESULTS: The median follow-up period was 30 months. The median progression-free survival was significantly longer with MPR-R (31 months) than with MPR (14 months; hazard ratio, 0.49; P<0.001) or MP (13 months; hazard ratio, 0.40; P<0.001). Response rates were superior with MPR-R and MPR (77% and 68%, respectively, vs. 50% with MP; P<0.001 and P=0.002, respectively, for the comparison with MP). The progression-free survival benefit associated with MPR-R was noted in patients 65 to 75 years of age but not in those older than 75 years of age (P=0.001 for treatment-by-age interaction). After induction therapy, a landmark analysis showed a 66% reduction in the rate of progression with MPR-R (hazard ratio for the comparison with MPR, 0.34; P<0.001) that was age-independent. During induction therapy, the most frequent adverse events were hematologic; grade 4 neutropenia was reported in 35%, 32%, and 8% of the patients in the MPR-R, MPR, and MP groups, respectively. The 3-year rate of second primary tumors was 7% with MPR-R, 7% with MPR, and 3% with MP. CONCLUSIONS: MPR-R significantly prolonged progression-free survival in patients with newly diagnosed multiple myeloma who were ineligible for transplantation, with the greatest benefit observed in patients 65 to 75 years of age. (Funded by Celgene; MM-015 ClinicalTrials.gov number, NCT00405756.)

Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma

BACKGROUND: The combination of bortezomib, melphalan, and prednisone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. Daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 706 patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation to receive nine cycles of bortezomib, melphalan, and prednisone either alone (control group) or with daratumumab (daratumumab group) until disease progression. The primary end point was progression-free survival. RESULTS: At a median follow-up of 16.5 months in a prespecified interim analysis, the 18-month progression-free survival rate was 71.6% (95% confidence interval [CI], 65.5 to 76.8) in the daratumumab group and 50.2% (95% CI, 43.2 to 56.7) in the control group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.38 to 0.65; P&amp;lt;0.001). The overall response rate was 90.9% in the daratumumab group, as compared with 73.9% in the control group (P&amp;lt;0.001), and the rate of complete response or better (including stringent complete response) was 42.6%, versus 24.4% (P&amp;lt;0.001). In the daratumumab group, 22.3% of the patients were negative for minimal residual disease (at a threshold of 1 tumor cell per 105 white cells), as compared with 6.2% of those in the control group (P&amp;lt;0.001). The most common adverse events of grade 3 or 4 were hematologic: neutropenia (in 39.9% of the patients in the daratumumab group and in 38.7% of those in the control group), thrombocytopenia (in 34.4% and 37.6%, respectively), and anemia (in 15.9% and 19.8%, respectively). The rate of grade 3 or 4 infections was 23.1% in the daratumumab group and 14.7% in the control group; the rate of treatment discontinuation due to infections was 0.9% and 1.4%, respectively. Daratumumabassociated infusion-related reactions occurred in 27.7% of the patients. CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for stemcell transplantation, daratumumab combined with bortezomib, melphalan, and prednisone resulted in a lower risk of disease progression or death than the same regimen without daratumumab. The daratumumab-containing regimen was associated with more grade 3 or 4 infections. (Funded by Janssen Research and Development; ALCYONE ClinicalTrials.gov number, NCT02195479). Copyright © 2017 Massachusetts Medical Society

Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial

Background: Standard-of-care treatment for patients with newly diagnosed multiple myeloma includes combination therapies for patients who are not eligible for autologous stem-cell transplantation. At the primary analysis for progression-free survival of the phase 3 ALCYONE trial, progression-free survival was significantly longer with daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) alone in patients with transplant-ineligible, newly diagnosed multiple myeloma. Here we report updated efficacy and safety results from a prespecified, interim, overall survival analysis of ALCYONE with more than 36 months of follow-up. Methods: ALCYONE was a multicentre, randomised, open-label, active-controlled, phase 3 trial that enrolled patients between Feb 9, 2015, and July 14, 2016, at 162 sites in 25 countries across North America, South America, Europe, and the Asia-Pacific region. Patients were eligible for inclusion if they had newly diagnosed multiple myeloma and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation, because of their age (≥65 years) or because of substantial comorbidities. Patients were randomly assigned in a 1:1 ratio and by permuted block randomisation to receive D-VMP or VMP. An interactive web-based randomisation system was used. Randomisation was stratified by International Staging System disease stage, geographical region, and age. There was no masking to treatment assignments. All patients received up to nine 6-week cycles of subcutaneous bortezomib (1·3 mg/m2 of body surface area on days 1, 4, 8, 11, 22, 25, 29, and 32 of cycle one and on days 1, 8, 22, and 29 of cycles two through nine), oral melphalan (9 mg/m2 once daily on days 1 through 4 of each cycle), and oral prednisone (60 mg/m2 once daily on days 1 through 4 of each cycle). Patients in the D-VMP group also received intravenous daratumumab (16 mg/kg of bodyweight, once weekly during cycle one, once every 3 weeks in cycles two through nine, and once every 4 weeks thereafter as maintenance therapy until disease progression or unacceptable toxicity). The primary endpoint was progression-free survival, which has been reported previously. Results presented are from a prespecified interim analysis for overall survival. The primary analysis population (including for overall survival) was the intention-to-treat population of all patients who were randomly assigned to treatment. The safety population included patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02195479. Findings: 706 patients were randomly assigned to treatment groups (350 to the D-VMP group, 356 to the VMP group). At a median follow-up of 40·1 months (IQR 37·4–43·1), a significant benefit in overall survival was observed for the D-VMP group. The hazard ratio (HR) for death in the D-VMP group compared with the VMP group was 0·60 (95% CI 0·46–0·80; p=0·0003). The Kaplan-Meier estimate of the 36-month rate of overall survival was 78·0% (95% CI 73·2–82·0) in the D-VMP group and 67·9% (62·6–72·6) in the VMP group. Progression-free survival, the primary endpoint, remained significantly improved for the D-VMP group (HR 0·42 [0·34–0·51]; p&amp;lt;0·0001). The most frequent adverse events during maintenance daratumumab monotherapy in patients in the D-VMP group were respiratory infections (54 [19%] of 278 patients had upper respiratory tract infections; 42 [15%] had bronchitis, 34 [12%] had viral upper respiratory tract infections), cough (34 [12%]), and diarrhoea (28 [10%]). Interpretation: D-VMP prolonged overall survival in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. With more than 3 years of follow-up, the D-VMP group continued to show significant improvement in progression-free survival, with no new safety concerns. Funding: Janssen Research &amp;amp; Development. © 2020 Elsevier Lt