Why doesn't a that-clause follow "in spite of"?
Solution 1:
Your question incorrectly presupposes two things:
1st presupposition:
A preposition such as of takes as complement only a noun phrase (a phrase headed by a noun).
Although a preposition typically takes a noun phrase, it doesn't always do. Here are some counterexamples:
a. get out of here
b. of late
c. in spite of me not having studied much for the exam
None of the emboldened complements of the preposition of is a noun phrase.
Now, if you're to argue that me not having studied much for the exam is indeed quite similar in function to a noun phrase, albeit not exactly a noun phrase, that's where your second incorrect presupposition comes in:
2nd presupposition:
A that-clause such as that I hadn't studied much for the exam is often called "a nominal clause" or even "a noun clause" simply because its function is considered to be similar to that of a noun phrase. Therefore, a that-clause must be allowed wherever a noun phrase is allowed.
Wrong!
Note that the emboldened word is similar, not identical. And the complement of a preposition is a function of a noun phrase, but not of that-clause.
If you hadn't presupposed these two things, I don't think you would have had any reason to ask the question in the first place.