Exclude posts with certain meta data from search results

First, the pre_get_posts hook is an action and not a filter.

Then the meta_query parameter should contain the relation only if there is more than one inner meta_query array (codex).

Finally you do not need to return the $query argument as it is passed by reference to your callback function.

Your code should look like this:

function ZoekGeenLegeItems( $query ) {
    if( is_admin() || !$query->is_search() || $query->get( 'post_type' ) != 'item' )
        return;

    $query->set('meta_query', array(
        array(
            'key'   => 'KEY_itm_leeg',
            'value' => '0'
        )
    ) );
}
add_action('pre_get_posts','ZoekGeenLegeItems');