A Phase II, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with Beta-Thalassemia Major

We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to 1000 mu g/L; cardiac MRI T2* = 5 mg/g). Patients received deferasirox at an initial dose of 10 mg/kg/day, with up-titration to a maximum of 20 mg/kg/day. The study continued for 52 weeks and included a total of 27 patients (mean age, 9.1 +/- 3.8 years; 70.4% male). One patient (3.7%) was lost to follow-up. The majority of patients (n = 20; 74.1%) were able to achieve the intended dose of 20 mg/kg/day. No deaths occurred. A total of 134 adverse events (AEs) were reported in 25 patients (92.6%) during the study. The majority of patients had grade 1 or 2 AEs, with only 8 patients (29.6%) experiencing grade 3 AEs. Only 10 AEs occurring in 4 patients (14.8%) were suspected to be related to deferasirox (ALT/AST increase, n = 4; urinary tract infection, n = 1). The deferasirox dose had to be adjusted or interrupted for 6 AEs occurring in 4 patients (14.8%). A total of 6 serious AEs occurred in 3 patients (11.1%), none of which were suspected to be related to deferasirox. From baseline to week 52, there were decreases in median concentrations of alanine aminotransferase (ALT), from 30.0 to 17.0 IU/L, and aspartate aminotransferase (AST), from 35.5 to 26.0 IU/L. Median serum creatinine and cystatin C concentrations were similar at baseline and week 52. There was a continuous and significant decrease in median serum ferritin level from 1718.0 mu g/L at baseline to 845.3 mu g/L following 52 weeks of therapy (P<.001); 9 patients (33.3%) achieved a level of <500 mu g/L. There was also a significant decrease in median LIC (from 8.6 to 4.1 mg/g; P<.001) and an increase in median cardiac T2* (from 26.0 to 28.0 ms; P=.520) from baseline to week 52. Our findings indicate that deferasirox treatment at doses up to 20 mg/kg/day reduces the iron burden in children with TM post-HSCT, with a manageable safety profile. (C) 2017 American Society for Blood and Marrow Transplantation.WoSScopu

A Phase II, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with beta-Thalassemia Major

We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to <18 years with beta-thalassemia major (TM) who underwent hematopoietic stem cell transplantation (HSCT) and had evidence of iron overload (serum ferritin >1000 mu g/L; cardiac MRI T2{*} <20 ms, or liver iron concentration {[}LIC; by MRI R2] >= 5 mg/g). Patients received deferasirox at an initial dose of 10 mg/kg/day, with up-titration to a maximum of 20 mg/kg/day. The study continued for 52 weeks and included a total of 27 patients (mean age, 9.1 +/- 3.8 years; 70.4\% male). One patient (3.7\%) was lost to follow-up. The majority of patients (n = 20; 74.1\%) were able to achieve the intended dose of 20 mg/kg/day. No deaths occurred. A total of 134 adverse events (AEs) were reported in 25 patients (92.6\%) during the study. The majority of patients had grade 1 or 2 AEs, with only 8 patients (29.6\%) experiencing grade 3 AEs. Only 10 AEs occurring in 4 patients (14.8\%) were suspected to be related to deferasirox (ALT/AST increase, n = 4; urinary tract infection, n = 1). The deferasirox dose had to be adjusted or interrupted for 6 AEs occurring in 4 patients (14.8\%). A total of 6 serious AEs occurred in 3 patients (11.1\%), none of which were suspected to be related to deferasirox. From baseline to week 52, there were decreases in median concentrations of alanine aminotransferase (ALT), from 30.0 to 17.0 IU/L, and aspartate aminotransferase (AST), from 35.5 to 26.0 IU/L. Median serum creatinine and cystatin C concentrations were similar at baseline and week 52. There was a continuous and significant decrease in median serum ferritin level from 1718.0 mu g/L at baseline to 845.3 mu g/L following 52 weeks of therapy (P<.001); 9 patients (33.3\%) achieved a level of <500 mu g/L. There was also a significant decrease in median LIC (from 8.6 to 4.1 mg/g; P<.001) and an increase in median cardiac T2{*} (from 26.0 to 28.0 ms; P=.520) from baseline to week 52. Our findings indicate that deferasirox treatment at doses up to 20 mg/kg/day reduces the iron burden in children with TM post-HSCT, with a manageable safety profile. (C) 2017 American Society for Blood and Marrow Transplantation

Frontline Nilotinib Treatment In Turkish Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia In Chronic Phase: Updated Results With 2 Years Of Follow-Up

Objectives: This report presents final results (24 months of follow-up) from the first prospective, national study of frontline nilotinib in chronic myeloid leukemia (CML) patients in Turkey. Methods: Patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase (CML-CP; N = 112) received nilotinib 300 mg twice daily. The primary endpoint, which was the cumulative rate of major molecular response (MMR; BCR-ABL1 <= 0.1% on the International Scale [BCR-ABL1(IS)]) by 12 months, was previously reported (66.1% [80% CI, 59.7%-72.0%]). ClinicalTrials.gov identifier NCT01274351 Results: By 24 months, 83.0% of patients achieved MMR, and 50.9% achieved MR4.5 (BCR-ABL1(IS) <= 0.0032%). Safety results at 24 months were consistent with those at 12 months. No additional deaths or disease progressions to accelerated phase/blast crisis were observed between 12 and 24 months. Discussion: Treatment with nilotinib 300 mg twice daily for 2 years provided high MMR with a good safety/tolerability profile in newly diagnosed CML-CP patients in Turkey. Assessment of MMR across time points showed increasing rates through 18 months, after which as lower rate of increase was observed. The safety profile of nilotinib 300 mg twice daily with 24 months of follow-up was similar to that observed at 12 months, and no new safety concerns were identified. These efficacy and safety findings are consistent with the results from the 12-month analysis of this study and from previous nilotinib studies. These findings support nilotinib as an option for frontline treatment of CML-CP. Conclusion: Frontline nilotinib treatment provided sustained efficacy, with good tolerability, over 24 months in newly diagnosed CML-CP patients.WoSScopu

Nilotinib Results in Improved Rates of Molecular Response in Turkish Newly Diagnosed CML-CP Patients: A 24-Month Update

WOS: 00034924270121

Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase

WOS: 000384401200003PubMed ID: 27501474Objective: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL10.1% on the International Scale [BCR-ABL1(IS)]) by 12months.Methods: Patients with newly diagnosed CML-CP were treated with nilotinib 300mg twice daily. This analysis was based on the first 12months of follow-up in a 24-month study.Results and Conclusions: Of 112 patients enrolled, 66.1% (80% CI, 59.7-72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR4.5 (BCR-ABL1(IS) 0.0032%) by 12months. During the first year of treatment, 1 patient progressed to blast crisis and 2 patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. These results support the use of nilotinib 300mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP.Novartis Pharmaceuticals CorporationNovartisThis study was funded by Novartis Pharmaceuticals Corporation