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FDA Grants Priority Review to Midostaurin for Acute Myeloid Leukemia
The U . S . Food and Drug Administration ( FDA ) granted priority review to midostaurin for adults with newly diagnosed FLT3- mutated acute myeloid leukemia ( AML ) or advanced systemic mastocytosis ( SM ).
The decision was based on the results of the phase II RATIFY trial of patients with AML and a single-arm , open-label , phase II study of patients with SM .
In the RATIFY trial , 717 patients were randomized to receive standard “ 7 + 3 ” induction and consolidation chemotherapy with daunorubicin and cytarabine , plus oral midostaurin 50 mg ( n = 360 ) or placebo ( n = 357 ). After four cycles of consolidation , maintenance therapy with either midostaurin or placebo was administered for up to one year . The addition of midostaurin to standard chemotherapy reduced the risk of death by 23 percent compared with chemotherapy alone : overall survival ( OS ; primary endpoint ) was 74.7 months with midostaurin versus 25.6 months with chemotherapy alone ( hazard ratio [ HR ] = 0.77 ; p = 0.0074 ). The fiveyear OS rate for patients in the midostaurin group was 50.9 percent compared with 43.9 percent receiving placebo . Grade ≥3 adverse events ( AEs ) were similar between the treatment cohorts .
In the SM trial , 116 patients received midostaurin 100 mg twice daily . The overall response rate ( ORR ) was 60 percent ( 95 % CI 49-70 ); 45 percent of patients had a major response ( defined as a complete resolution of at least one type of mastocytosis-related organ damage ). The median OS was 28.7 months , and the median progression-free survival ( PFS ) was 14.1 months . AE-related dose reductions occurred in 56 percent of the patients . Nausea , vomiting , and diarrhea were the most common treatment-related
AEs . Grade 3 / 4 neutropenia , anemia , and thrombocytopenia were also reported .
Sources : Novartis press release , November 14 , 2016 ; Gotlib J , Kluin- Nelemans HC , George TI , et al . Efficacy and safety of midostaurin in advanced systemic mastocytosis . N Engl J Med . 2016 ; 374:2530-41 .
HHS and NIH Announce New Requirements for Clinical Trials in an Effort to Improve Access and Data Sharing
The U . S . Department of Health and Human Services ( HHS ) and the National Institutes of Health ( NIH ) announced new requirements for registering and reporting clinical trial results on ClinicalTrials . gov , and reporting those results to the public . HHS hopes to increase the number of patients with cancer who participate in clinical trials , as many clinical trials fail because they do not meet enrollment targets and cannot provide meaningful results on a potential treatment . The policy changes were created to help patients and practitioners locate appropriate clinical trials , with some new rules including :
• requiring that clinical trials be registered on ClinicalTrials . gov within 21 days of enrolling the first participant
• requiring that clinical trial results be published within 12 months of collecting the last data point – for trials with both positive and negative outcomes
• withholding funding to institutions that receive federal grants for clinical trials that are not adequately registered or reported on
“ We are going to expect applicants who are generating data sets to produce a data-sharing plan or we are not going to fund them .”
— FRANCIS COLLINS , MD , PhD
• allowing third-party sites to provide information to their constituencies through a new application programming interface that allows patient advocacy groups , cancer centers , and researchers to build web applications and search engines to improve access to clinical trial information
These rules do not extend to smaller trials such as phase I and feasibility studies . The rules were developed based on the 900 comments received during a public comment period . Read the HHS final rule at s3 . amazonaws . com / public-inspection . federalregister . gov / 2016-22129 . pdf .
The NIH also announced that it will require researchers who receive federal funding from the agency to submit a plan outlining how data gleaned from the government-backed project will be shared with the public . Open data-sharing is a tenet of Vice President Joe Biden ’ s Cancer Moonshot Initiative , which strives to increase access to clinical trials and encourage data sharing as part of its mission .
“ We are going to expect applicants who are generating data sets to produce a data-sharing plan or we are not going to fund them ,” said NIH Director Francis Collins , MD , PhD . “ And for applicants who have failed to live up to their responsibilities for data sharing , that will hurt them in their next opportunity to get funds from NIH .”
Dr . Collins did not provide a firm date for when the new policy would be implemented across the agency , but said that NIH is in the “ middle of figuring out how to regularize that ” across the different NIH centers .
Data sharing has become a controversial topic recently , raising questions about accuracy , authenticity , and ownership . The editors of the New England Journal of Medicine , for example , introduced the concept of “ research parasites ” earlier this year in an editorial claiming that open sharing of data could lead to scientists using another group ’ s data for their own gain .
Source : National Institutes of Health news release , September 16 , 2016 and November 3 , 2016 .
FDA Approves Daratumumab Combination for Multiple Myeloma
The FDA approved daratumumab in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for patients with multiple myeloma who have received at least one prior therapy .
The approval was based on the results of two randomized , open-label trials . The CASTOR trial evaluated daratumumab in combination with bortezomib and dexamethasone compared with bortezomib and dexamethasone alone . Adding daratumumab to treatment resulted in a 61 percent reduction in the risk of disease progression or death ( HR = 0.39 ; 95 % CI 0.28-0.53 ; p < 0.0001 ); the median PFS was not reached in the daratumumab combination cohort , compared with 7.2 months in the bortezomib and dexamethasone alone cohort . The addition of daratumumab also resulted in an increased ORR : 83 percent versus 63 percent ( p < 0.0001 ).
The most common treatment-related AEs in the CASTOR trial included infusion-related reactions ( IRRs ), diarrhea , peripheral edema , upper respiratory tract infection , peripheral sensory neuropathy , cough , and dyspnea .
The POLLUX trial evaluated daratumumab in combination with lenalidomide and dexamethasone compared with lenalidomide and dexamethasone . The daratumumab combination therapy resulted in a 63 percent reduction in the risk of disease progression or death compared with lenalidomide and dexamethasone alone ( HR = 0.37 ; 95 % CI 0.27-0.52 ; p < 0.0001 ); the median PFS was not reached in the daratumumab combination cohort compared with 18.4 months for those who received lenalidomide and dexamethasone alone . The addition of daratumumab also significantly increased ORR : 93 percent versus 76 percent ( p < 0.0001 ).
The most common treatment-related AEs in the POLLUX trial included IRRs , diarrhea , nausea , fatigue , pyrexia , upper respiratory tract infection , muscle spasm , cough , and dyspnea .
Daratumumab carries a warning for neutropenia and thrombocytopenia .
Source : Janssen press release , November 21 , 2016 .
Mixed Results for Fostamatinib in Studies of Immune Thrombocytopenia
Data from two double-blind studies of the SYK inhibitor fostamatinib in adult patients with chronic / persistent immune thrombocytopenia ( ITP ) showed disparate results . Combined data , however , suggested that fostamatinib was associated with a better platelet response than placebo .
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