Phase 3 Canines Lymphoma B Trial ( what to expect)

Hi all,

The debrief by PAA the other day gave a hint of what we will see in the upcoming Phase 3 trial.

These are my interpretations.

What was mentioned is that Dr Cannon ( previous chief investigator ) has left PAA for a private enterprise that is not geared for doing trials. We thus employed Dr Agnew as a worthy replacement.

Dr Agnew has reevaluated Phase 2b results and has decided on a multi armed Phase 3. We will get onto that later.

Before hand let's refresh what exactly is B cell Lymphoma. Now imagine your immune system. It finds a pathogen or a bug and sends it's team of fighters into the fray to negate said pathogen. The B cell is like the Army Transport Corp. It provides transport by its cellular membranes to the war zone. Once at the war zone it unloads fighting T killer cells from its membrane to negate or hopefully negate the pathogen. Imagine an Armoured Personnel Carrier opening its doors and all the T cells come out the back. Without that the T cells are stuck at base. So B cells are important.

B Cells die a natural death in the body lasting maybe 4 months. They are made in the bone marrow and lymph node. When dogs get older ( certain breeds) the reproduction of the B cells can be mutated and cause a Cancer.
The B cells when mature change their molecular make up in the Spleen. Thus if mutated Cancer is developed the Spleen becomes infected as well as the Lymph nodes ( think of those two are Army bases).

One of the first clinical signs of B cell Lymphoma is swelling Lymph nodes and the Spleen.

Now we have heard before of T Cell Lymphoma. What is the difference and why can Monepantel ( MPL) be of benefit. T cell Lymphoma is deadlier in Canines than B cell Lymphoma . Data suggests a dog with T cell Lymphoma who is having chemotherapy may survive 8months compared to B cell 12 to 15months. T cells as said before are one of our active pathogen fighting cells also ( the cause of cancer is unknown , but may be linked to HTLV-1 see below announcement ) . They are also made in the bone marrow and once mature gravitate to the thymus. T cells are more active in the body due to the way they invade a pathogen cell. They tend to get exhausted quicker than B cells, and possibly due to that fact may mutate into Cancer cells moreso than B cell. Now according to a PAA announcement 12/07/2021 and because of PAA was getting Monepantel laboratory tested for Covid 19, we have a glimpse of the future,in that we have a compound that can fight some T cell Cancers.

Onto the Dog trial. What can be done to combine therapies to make a huge difference in tumour size and progressive survival?

One , the administration of Prednisone with MPL will be beneficial. Prednisone metabolizes to Prednisolone in the body. It is an anti inflammatory and studies have shown that giving Prednisone alone can increase a dog's life by 3 to 4 months, and in some cases the tumour is resolved. Prednisone has an added effect of increasing appetite and energy output.

Two, the combination of MPL with Gemcitabine will also works possibly better than number 1. Gemcitabine studies alone show can reduce tumour size by 17%.Thus its main attribute is regression of tumour size.

Three , Cistplatin ( affects the DNA replication of the cancer cells) with alone studies showing dead cancer cell by 30% after 4 days. All three combinations can be used in Canines and humans alike.

Gncitabine and Cistplatin were both mentioned in Veterinarian Science Week where Dr Mollard presented his Phase 2b data.

But , to date they haven't been mated with MPL. My thoughts are we have to weigh side effects with longetivity. Both Cisplatin and Gemcitabine have side effects and both are non patented. But, both will or should work in synergy. Drug combinations are fraught with adverse effects. Do we go for the whole show and combine all four. Would it work, I feel it would but would the side effects break one's heart. Dogs only live a certain amount of time unfortunately. Or do we just combine MPL with Prednisone for an easier journey?

Which ever way Dr Agnew feels, I am sure we are into something special for our best mates. Not forgetting that all this data corresponds to human cancer.

The delay in supplies was mentioned as fortuitous by Dr Mollard in their last briefing. He went on to say it gives them more time to place strategies in place for our next trial.

Cheers kpax.