Cel Sci Corporation (CVM)

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Some small useful tidbits I've found. Some of which have not been discussed:

For the Stat Guys:
Study size and power has been discussed ad naseum. Here are some specifics.

From the Clinical Trial Site (https://clinicaltrials.gov/ct2/show/record/NCT01265849)
OS will be assessed using Kaplan-Meier life-table and compared using a logrank test and confirmed further with tumor stage location and geographic stratified log rank tests. The unstratified logrank test constitutes the primary analysis.

An Article Titled: "Power Loss of Stratified Log-Rank Test in Homogeneous Samples"
(https://www.hindawi.com/journals/jqre/2010/942184/)

"This shows that the ULRT (Unstratified Log-Rank Test) is asymptotically slightly more powerful than its SLRT (Stratified Log-Rank Test) counterpart.

"It is well known in survival analysis that the (unstratified) log-rank test (ULRT) is the most efficient invariant test under contiguous alternatives in the proportional hazards model"

We are using the Unstratified log-rank test which gives us more statistical power in our final analysis which is a positive. CVM has thought this out and chosen the best one for our P value over time.

Dropouts and Futility:

Going along with that, from the clinical trial site it specifically says "Interim analyses will be performed throughout the study to assess safety, sample size and futility."

Right there, for anyone who questions why dropouts shouldn't be an issue. If they were, this would've been caught when the IDMC has met bi-annually to assess for sample size and futility.

Okay now onto the new discussion on CIZ which I personally think has been overlooked drastically by all of us.


CIZ Combination:

"in Phase 1 and 2 clinical trials. LI(Multikine) was administered prior to SOC and in combination with low non-chemotherapeutic doses of cyclophosphamide, indomethacin, and zinc(CIZ) in studies with LI."

So on the phase 1 and 2 trials they got a 33% survival increase by combining Multikine and a daily dose of Zinc vitamin with LOW NON-CHEMOTHERAPEUTIC DOSES of cyclophosphmide and Indomethacin. They are doing the same in the test arm in this Phase 3 trial as well. I think the CIZ combination is nothing to scoff at.

Leukocyte Interleukin Injection (LI)[Multikine] contains a defined mixture of naturally derived cytokines and chemokines with demonstrated safety and immunomodulatory activity in animals and in man in Phase 1 and 2 clinical trials. LI was administered prior to SOC and in combination with low non-chemotherapeutic doses of cyclophosphamide, indomethacin, and zinc(CIZ) in studies with LI. The results of these studies indicate that the local/regional injection of mixed interleukins (LI) with CIZ prior to SOC can overcome local immunosuppression, break tumor tolerance to tumor antigens and allow for a sustainable and effective anti-tumor immune response.

Wow! This is a combination with Multikine as the secret ingredient to make them all work best together.

So what are these three additional drugs?

Indomethacin: Nonsteroidal anti-inflammatory drug. It can treat pain.

Cyclophosphmide: This is an immunosuppressive drug/chemotherapy. It can treat cancer, including leukemia and lymphomas. (They have lowered the dosage which I presume gives benefits while not suppressing the immune system as much while combining it with Zinc which is next on our list)

Zinc: Zinc is a mineral. It is called an "essential trace element" because very small amounts of zinc are necessary for human health. Since the human body does not store excess zinc, it must be consumed regularly as part of the diet. Zinc is needed for the proper growth and maintenance of the human body. It is found in several systems and biological reactions, and it is needed for immune function, wound healing, blood clotting, thyroid function, and much more.

I have not seen anyone ever comment on this topic on any board. But because of COVID-19 I've seen a lot of articles about why people should be taking Zinc to boost their immune systems. Zinc is now sold out whenever I go to the store.

From the Clinical Trial Site Under the Intervention Details:
Dietary Supplement: Zinc
One capsule daily beginning on day one of treatment with LI until one day before surgery

For the third arm of the study LI(Multikine) is administered without CIZ to determine the contribution of CIZ (Cyclophosphmide, Indomethacin, and Zinc) to the effects of LI(Multikine). This third arm now makes complete sense to me, they want to see if Multikine is MORE effective when combined with those three other drugs. I presume this third arm will probably not perform as well as our main Multikine arm. And for those who already have the thought of "WEll it's the CIZ that's making the difference." That is idiotic thinking. The CIZ would be not much use if not combined with Multikine. It's the Multikine that is making the CIZ more powerful if this works.

Not only that but it's not like they give these patients Multikine once a week for 3 weeks. They give them an intense regimen.
"LI 400IU (2.0mL total daily) 1.0 mL peritumoral, 1.0 mL perilymphatic (aka Multikine) is given 5x weekly for 3 weeks administered in combination with cyclophosphamide indomethacin and zinc (CIZ) as adjuvant therapy prior to SOC

Summary:
Even us diehard longs sometimes get tired out and forget or don't fully understand how complicated and legitimate of a treatment process CVM has come up with for their patients. This isn't some scam. This is a serious combination of well thought out drugs and dosages to give patients. Most of us are not scientists but the more time I spend really trying to understand and read in depth the more I understand that Cel-Sci is not messing around. Whether this ends up working or not is still to be determined. But the team at CVM is dead serious about their treatment regimen and have poured a lot of hard work and thought into this.

The more we understand about this study the better.

Open to thoughts and discussion.