Replies to post #54687 on NorthWest Biotherapeutics Inc (NWBO)

[Poor Man -]

For a new investor, I'm very curious how the crossover process works, while the patient remains blinded to the doctors treating the patient?

[Evaluate]

Still unclear what happens when a treatment arm patient 'crosses over'.
Do they 'reset the clock' or just continue dosing regimen? (I'm unclear). Do they employ placebo at all after crossover? --- longfellow95

In order to maintain the blind, it is my understanding that when a patient progresses & accepts the crossover option ... that they do start their treatment protocol as if they were back at day one.
If they only did this accelerated protocol with a patient that crossed over from the placebo arm, but not for a patient that crossed over from the treatment arm, then the doctors & patients would quickly realize which arm they were in prior to crossing over. In order to keep the blind, they start all patients at the beginning of treatment protocol after crossing over.
So they 'do not just continue dosing regimen", but instead "reset the clock" (to put it in your words).

Do they employ placebo after crossover?
First part of the answer would be that they do not employ the placebo IMMEDIATELY after crossover. Instead, they inject the real vaccine immediately after crossover .... until the patient has no remaining real vaccine left over for injections.
This is of course less likely to happen to a patient who crossed over from the placebo arm, since he/she would not have used up any of his/her real vaccine yet.
It is my understanding that a patient who starts in the treatment arm, and then progresses, and then accepts the crossover option, and continues to receive his/her real vaccine until it runs out .... I get the impression that for this patient it might hold true that he/she winds up possibly getting some placebo vaccine at the tail end of the trial to maintain the blind.
Up to the 3 year mark, I believe.

[flipper44]

See the old protocol RK posted in message # 52892.

They reset the dosing clock when treatment patients crossover, because no one knows if they were placebo or treatment arm. This means they get more frequent dosing again.

It does not look, after reading RK's message # 52892, that any placebo would be used after patient crossover, IMHO.

[Stillwell888]

From Cancer UK website:

The trial team will talk to you about joining the trial before you have surgery. This is because they need your permission to get samples of your tumour that they would be able to use to make the vaccine.

Agreeing to this doesn’t mean that you will definitely be able to take part in the trial. Whether or not you can take part depends on the results of MRI scans after surgery and radiotherapy, whether the researchers are able to get enough material from your tumour to make the vaccine, and other factors.

If it turns out that you can’t take part in the trial, the sample of your brain tumour will be used for research, unless you tell the trial team that you want it to be destroyed instead.

If it looks as though you can take part in the trial, the next step is for the researchers to get some of your white blood cells to make the vaccine. The way they do this is described in the hospital visits section below.

You then have radiotherapy and chemotherapy. After finishing radiotherapy, you have another MRI scan to check that your tumour hasn’t started growing again. You can only take part in this trial if your doctors are sure that your tumour hasn’t started to grow again.

Sometimes, it isn’t possible to tell from the results of a scan whether or not a tumour has started growing again. It may look as though there is growth, but it could be swelling (inflammation) or scarring after surgery. If the doctors are unsure what the results are showing, you have another MRI scan 2 months later. If this shows there is no growth, you may then be able to take part in the trial.

The trial is randomised. The people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. And neither of you will know which group you are in. This is called a double blind trial.

For every 3 people who take part, 2 have DCVax-L injections and 1 has a dummy injection (placebo Open a glossary item).

DCVax-L for glioblastoma multiforme trial diagram

You have the vaccine (or dummy) injections under the skin on your upper arm. You have them 3 times in the first month, 4 more times over the next year and then every 6 months until the end of treatment. You have 2 separate injections each time.

If scans show that your tumour starts to grow again during treatment, you can start having DCVax-L injections regardless of the group you are in. This is called a ‘crossover option’. You may have already been having the vaccine, or you may have been having the dummy drug – neither you nor your doctor will know. If you go into the crossover option, you still won’t know which treatment you’d been having up until then. But you will definitely be having the vaccine from then on.

Your doctor will tell you if your tumour has started to grow again and then it is your choice whether you want to definitely start having the vaccine or not.

If you do, you start the treatment from the beginning, so you have the vaccine 3 times in the next month, 4 more times over the next year and then every 6 months. You may have other treatment as well if your doctor thinks it is right for you.