FDA Recommends Expanding Clinical Trial Eligibility for Patients With Incurable Cancers
The FDA has issued draft guidance for expanding investigational clinical trial options for patients with incurable cancers , encouraging sponsors to waive rules requiring patients to have undergone multiple existing alternative therapies to enroll .
“ The FDA believes patients with incurable cancers , if provided adequate information to make an informed decision , should be eligible to participate in oncology clinical trials ,” said Richard Pazdur , MD , director of the agency ’ s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA ’ s Center for Drug Evaluation and Research . “ If there is no scientific rationale for excluding these patients , then clinical trial eligibility criteria should be broadened to include these patients , with appropriate informed consent ,” he said .
When finalized , the document , “ Cancer Clinical Trial Eligibility Criteria : Available Therapy in Non-Curative Settings ,” will provide recommendations for expanding eligibility for patients with incurable cancers , including evaluating patients who have not received available therapies in separate cohorts from those who have . Source : FDA press release , June 24 , 2021 .
Dabigatran Etexilate Approved for Children With VTE
The U . S . Food and Drug Administration ( FDA ) has approved dabigatran etexilate oral pellets for the treatment of children ages three months to 12 years with venous thromboembolism ( VTE ) directly after receiving injectable anticoagulants for at least five days . The treatment also is approved as prophylaxis for recurrent thrombosis in patients ages three months to 12 years who have completed treatment for first VTE .
This approval is based on safety and efficacy data from a study of 267 pediatric patients who were randomly assigned to receive either dabigatran etexilate or standard of care . The primary composite endpoint consisted of the proportion of patients with complete thrombus resolution , as well as freedom from recurrent VTE and VTE-related death . Of the 177 patients treated with dabigatran etexilate , 81 ( 46 %) met the composite endpoint , compared with 38 ( 42 %) of 90 patients receiving standard therapy .
“ The FDA is committed to helping our youngest patients with serious medical conditions have treatments that are relatively easy to take ,” said Ann Farrell , MD , director of the division of non-malignant hematology in the FDA ’ s Center for Drug Evaluation and Research . “ With [ the ] approval of [ dabigatran etexilate ], pediatric patients have another therapeutic option to treat and prevent potentially deadly blood clots .”
This indication includes a boxed warning cautioning that early treatment discontinuation may increase the risk of thrombosis , and that in patients undergoing spinal procedures , spinal or epidural hematomas may cause serious complications . As dabigatran etexilate can cause severe and fatal bleeding , it is not recommended for patients with bioprosthetic heart valves or triple-positive antiphospholipid syndrome .
Dabigatran etexilate is the first FDA-approved oral anticoagulant for children . In 2010 , the medication was approved to reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial
fibrillation . Sources : FDA press release , June 21 , 2021 ; Halton J , Brandão LR , Luciani M , et al . Dabigatran etexilate for the treatment of acute venous thromboembolism in children ( DIVERSITY ): A randomised , controlled , open-label , phase 2b / 3 , non-inferiority trial . Lancet Haematol . 2021 ; 8 ( 1 ): e22-e33 .
Orelabrutinib Receives Breakthrough Therapy Designation for MCL
The FDA has granted breakthrough therapy designation to the selective Bruton tyrosine kinase inhibitor orelabrutinib for the treatment of patients with relapsed / refractory mantle cell lymphoma ( MCL ).
This decision is based on results from a phase II trial ( NCT04014205 ) evaluating the safety and efficacy of oral orelabrutinib in 80 patients with B-cell malignancies , including relapsed / refractory chronic lymphocytic leukemia ( CLL )/ small lymphocytic lymphoma ( SLL ). At a median follow-up of 6.3 months ( range = 0.4-13.7 ), 78 patients were evaluable for response , with an overall response rate of 88.5 % ( n = 69 ). One patient achieved a complete response , while 39 had a partial response ( PR ) and 29 achieved PR with lymphocytosis . The six-month duration of response ( DOR ) rate was 89.8 %. Median DOR was not yet reached . Disease control rate was 96.2 %, with 7.7 % of patients experiencing disease stability .
Common grade ≥3 adverse events were neutropenia , thrombocytopenia , and lung infections . At least one serious toxicity was reported in 31 % of patients , including decreased platelet count ( n = 3 ), pneumonitis ( n = 2 ), pyrexia ( n = 2 ), and herpes zoster ( n = 1 ).
In December 2020 , orelabrutinib was approved by the China National Medical Products Administration for the treatment of patients with relapsed / refractory MCL and CLL / SLL . Source : Pharmacy Times , June 29 , 2021 .
Asparaginase Erwinia Chrysanthemi Approved for Leukemia / Lymphoma
Asparaginase Erwinia chrysanthemi ( recombinant ) - rywn has been approved by the FDA as part of a treatment regimen for adult and pediatric patients with acute lymphocytic leukemia ( ALL ) and lymphoblastic lymphoma ( LBL ) who have developed hypersensitivity to E . coli-derived asparaginase .
This decision is based on efficacy data from Study
JZP458-201 ( NCT04145531 ), which enrolled 102 patients ages 1 to 24 with ALL or LBL and hypersensitivity to E . coli-derived asparaginase within a chemotherapy regimen . Asparaginase Erwinia chrysanthemi was administered intramuscularly at various dosages . The primary endpoint of the study was the achievement and maintenance of nadir serum asparaginase activity above 0.1 U / mL . At a dosage of 25 mg / m 2 , 93.6 % of patients achieved the primary endpoint at 48 hours after administration .
Adverse events occurring in > 20 % of patients included abnormal liver test , nausea , musculoskeletal pain , fatigue , infection , headache , pyrexia , drug hypersensitivity , febrile neutropenia , decreased appetite , stomatitis , bleeding , and hyperglycemia .
Recommended dosage of asparaginase Erwinia chrysanthemi is 25 mg / m 2 administered intramuscularly every 49 hours for the required duration of asparaginase activity . Source : FDA press release , June 30 , 2021 .
One-Quarter of U . S . Covered Under Medicaid During the Pandemic
A recent government report revealed that nearly 10 million Americans enrolled in Medicaid during the COVID-19 pandemic , with a record 80 million people – one-quarter of the population – covered under the public health program . This represents a 14 % increase over the 12-month period ending January 31 , 2020 , and includes the Children ’ s Health Insurance Program , which covers children whose parents ’ incomes are too high to qualify for Medicaid but too low to allow them to afford alternative coverage .
“ This tells us that Medicaid is a critical program for American families ,” Chiquita Brooks-LaSure , Centers for Medicare & Medicaid Services administrator at the U . S . Department of Health and Human Services , told The New York Times . “ What we ’ ve seen during this pandemic is that people want access to affordable health insurance , and how important it is during a public health crisis .”
Medicaid , which was expanded in most U . S . states under the Affordable Care Act ( ACA ) in 2014 , covers all adults with income up to 138 % of the poverty level , or about $ 17,420 per individual this year . At the start of the COVID-19 pandemic , Congress provided a 6.2 % increase in Medicaid funding to prevent states from disenrolling patients or tightening eligibility requirements .
Twelve states , including Florida and Texas , declined to expand Medicaid under the ACA . Utah , Idaho , and Nebraska voted to expand their programs last year , and Oklahoma did the same in July .
During the pandemic , adult enrollment in Medicaid grew twice as fast as child enrollment , suggesting that job losses related to the public health crisis may have left many adults newly eligible for the program . Source : The New York Times , June 21 , 2021 .
24 ASH Clinical News August 2021