Note that the EventManager doesn't have an UnregisterClassHandler method. This is why it is recommended that the RegiesterClassHandler() method to be called in the static constructor of the page. This will apply the handler to all instances of the RadUploadItem only once.
Another approach that you can use it to register/unregister the event handler using the AddHandler method of the RadUpload control. Here is an example in code:
Let me know if you have any further questions.
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