A Patient Sponsored & Funded Clinical Trial Initiative by CLL Topics
June 25, 2004
by Chaya Venkat
Announcement of Two Key Developments
Today we crossed two important milestones in the development of Project Alpha.
Drum Roll Please - Here Comes the New Monoclonal Drug
We are finally at liberty to disclose the nature of the "mystery monoclonal" that will be used as the pivotal drug in Project Alpha. It is called "Avastin" and is made by Genentech, the same folks that have bought us Rituxan. Avastin is a brand new monoclonal antibody that has recently been approved by the FDA for colorectal cancer, where it showed actual survival advantage, somewhat surprising considering they recruited end-of-the-road patients for this clinical trial. I could have told you all this many months ago, but then I would have had to kill you. This way is better, don't you agree?
By now you are all familiar with the statement that Rituxan targets CD20 marker on CLL cells. Avastin targets a protein called VEGF (Vascular Endothelial Growth Factor). Those of you who are fans of Dr. Judah Folkman and his seminal work on angiogenesis will have no problem understanding the science behind blocking VEGF as a way of controlling cancer growth. If you wish, you can brush up on your understanding of angiogenesis, a process that is critical in the feeding and care of cancer cells, by browsing previous articles on the subject on our website: Do You Like Drinking Green Tea? Avastin is being put through its paces with many other cancers, the common theme being cancers that show a great deal of dependence on this VEGF based pathway for their growth and survival. Fortunately for us, CLL is one such cancer. Normally, we would have to wait many years while they tested every other cancer under the sun with this new and interesting drug, and CLL patients would be on the outside, their cold noses pressed to the window pane watching the "big" cancers get served first. Heck, we have become used to CLL clinical trials as an after thought, after Non-Hodgkin's lymphoma has had its turn as the significant B-cell malignancy. Not this time around!! For a change, this time around we are at the head of the queue. In the next few weeks I will be reviewing the science behind Avastin, and sharing with you my research findings of how it has fared in other clinical trials.
Just as in any drug sale there has to be a pusher and a buyer, every cancer that depends on VEGF protein also expresses appropriate receptors that bind to the VEGF. The protein and its receptors on cancer cells are the yin and yang, two perfectly mated pieces of the puzzle. These receptors (the acronym is VEGFR, where "R" is for receptor) are very highly expressed on CLL cells. The idea behind Project Alpha is not only to block the VEGF by using Avastin, but also to block the VEGFReceptors on the CLL cells - come at the problem from both ends, as it were. If you have not been asleep the past few months, I am sure you have guessed by now our favorite blocker of VEGFReceptors. It is none other than EGCG, the active ingredient of green tea.
You would be pleased to know that this clinical trial will be conducted under the auspices of the NCI. They will be supplying both the Avastin and the EGCG (in the capsule form, I am afraid. No one at the NCI is sufficiently into gourmet chocolate making, in fact I doubt they have even heard of Harvey's Chocolates.) Project Alpha will be an open label, Phase 2 multi-center trial, recruiting as many as 45 to 60 patients. The details are yet to be worked out, but my understanding is that this is now a pretty substantial trial, and will most likely recruit "chemo-naive" CLL patients across all risk categories. It is also my understanding that prior use of immunotherapy drugs such as Rituxan are not grounds for exclusion, so all you Rituxan fans can heave a sigh of relief.
There will be two pre-Project Alpha clinical trials kicked off in the near future, to verify safety and appropriate dosages of Avastin and EGCG as stand-alone drugs in CLL patients. I am sure you can understand, it is important to check out safety and dosage issues for each drug independently, before they are used in combination. Assuming that the the two single trials for Avastin and EGCG are showing all the right data we will be able to proceed to Project Alpha. While we will not be actively funding these pre-trials with our hard earned cash, CLL Topics nevertheless actively supports them and urge your participation if they fit your therapy needs. Many of you have expressed interest in green tea EGCG as a non-toxic approach to holding the CLL at bay, but at the same time have felt frustrated at the lack of formal guidance. Here is your chance. You will be well monitored, under the expert eye of some of the best CLL experts in the country, using EGCG formulations that have passed quality control requirements of the NCI. I do not know about you, but to my mind there is a great deal of safety in participating in an NCI sponsored clinical trial, conducted at top rated institutions like the Mayo Clinic. It does not get much safer than that.
Avastin is one hot monoclonal story these days. There were several articles in recent Business Week, Wall Street Journal and the like, specifically mentioning this particular drug. While it gets good press in terms of its potential efficacy, it also carries with it a hefty dollar price tag. It will be many moons before your friendly medical insurance company will gladly shell out hard cash for this drug, I heard dollar numbers in the region of $70,000 per person for full dose Avastin therapy. Here then is your chance to get into a clinical trial where the drug comes from the NCI, and you have access to it that would otherwise be impossible. Too bad PC and the other members of the Board of CLL Topics are not eligible to participate in Project Alpha, strictly to avoid even the appearance of nepotism.
Is there a fly in the ointment? You bet. Perhaps it is my less than patient nature, but time seems to march to a different beat when clinical trials are discussed. There are reams of paperwork, many layers of permissions and approvals to be obtained, prudence and caution that sends me around the bend. But, I will the first one to admit the prudence and caution are necessary, and as a patient advocate I will be first one screaming bloody murder if these safety precautions are short changed. I will update you as soon as I get a handle on the time frame of both the pre-trials, as well as the full fledged trial using both agents. Right now, there is too much uncertainty about timing and I do not want to feed you inaccurate information.
Project Alpha is a precious first experiment of its kind, we need to do this right, by the book. Hopefully the paperwork for the pre-trials with Avastin and EGCG as single agents will get done soon. My guess is that the patient recruitment will not pose a problem, not unless you consider too many people wanting to get in a problem. These two pre-trials will not carry the tag-line of our sponsorship, they were on the drawing board before Project Alpha was a wicked gleam in my eye. Project Alpha, the combination of these two pieces of the puzzle, Avastin and EGCG, that will be the one we sponsor with our money, our bodies and our grassroots patient support. Innovative clinical trial, sponsored by the NCI, Mayo Clinic, and CLL Topics. I think that has a nice ring to it, don't you?
Second Drum Roll Please - For Our Beloved IRS
That's right folks, we have just received their ruling on our tax-exempt status. We filed our request for this back on December 15 of last year and paid the $500 to get an advance ruling. Six months later, we have our ruling: the application was approved. Hey, I am not complaining. Glad we have it and better late than never. This approval confirms the tax deductibility of all your donations dating back to the incorporation of CLL Topics, Inc. Further, any of you who work for employers with matching charitable gift programs can now get us some extra cash from your employers. PC will be sending out an email to each of our donors spelling out the details. Please, if you do have this option, take the time to fill in the forms. Write if you need additional information or help with the process. We are not doing too badly on the fund raising front, we are past the half way mark already. If you have family or friends who might like to donate, Beth Weigand has a bunch of nice brochures that you can get from her, to send off to potential donors.
You can contribute to support our efforts.