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Dr. Neil Kay and
his research team do not need an introduction on this
website. Their article "Prognosis at Diagnosis" was reviewed
recently on CLL Topics, and it echoes our perspective in so
many ways. The Mayo Clinic Hematologic Malignancies program
has been at the forefront in defining modern prognostic
tests and risk stratification of CLL patients. Dr. Kay is a
member of the prestigious CLL Research Consortium and has
authored several important research papers on CLL, some in
collaboration with European CLL experts. Several of us have
met with Dr. Kay and his team in recent months, and came
away impressed. I have this theory, I think the cold air of
Minnesota winters has a special effect of up regulating
humanity and compassion, and down regulating business as
usual approach to medicine. Be that as it may, we are
delighted to be working with the Mayo team and Project Alpha
is in good hands with Dr. Kay as our Principal Investigator.
Over the past
few months since the original proposal for Project Alpha was
published on our website, we contacted many CLL experts for
their suggestions and guidance. Our own thoughts about the
design and goals of Project Alpha evolved as a result of
this feedback. Since Rituxan is getting lots of attention
anyway, we decided to use our money to sponsor other
promising biologics that might otherwise not get tested
soon. Recent reports about potential downside of
EPO
(read
our article on the topic) have made me a little cautious
about other hematopoietic growth factors such as GM-CSF.
Perhaps my caution is unwarranted, but it does not hurt to
be more prudent than otherwise with our first project. In
the final analysis, two specific projects have been
identified, and I would like to describe them briefly. More
details will be available later on, after the protocols are
fully fleshed out.
The first
project is a formal clinical trial for high risk and early
stage CLL patients, comprising of an immunotherapy drug
followed by a maintenance "cocktail" of chemopreventive
drugs to stabilize this poor prognosis sub-group. As you can
see, we have changed the subject group from good prognosis
patients to poor prognosis patients. There are three reasons
why this change was made in the clinical trial design for
Project Alpha and it was made based on serious discussions
with several experts.
(1) Low risk
patients are likely to live many years without needing
therapy. How can we prove our kinder and gentler approach to
therapy and patient-friendly remission maintenance has
actually made a difference? Since by historical norms, high
risk patients progress very rapidly and require therapy soon
after diagnosis, improvements will be easier to judge. Too
many early phase clinical trials are under-powered and their
very design makes their findings statistically suspect. We
wanted to be sure that does not happen to our project, that
the results of the Project Alpha clinical trial are
unequivocal, statistically significant and the design,
beyond reproach. This is crucial if we want to be able to
nurture our project through the regulatory hurdles.
I am sure many of you are as frustrated as I am in the time
it takes to translate a brilliant idea from the lab to a
commercially available therapy option that patients can use.
(2) Equally
important, to put it rather bluntly high risk "Bucket C"
patients need the help most, and sooner the better.
Furthermore, they need to be in early stage because poor
prognosis patients, after they have been through the wars of
several bouts of heavy duty chemotherapy, are not good
candidates for fine tuned biologic and immunotherapy
approaches.
(3) Last but not
least, if these innovative approaches work with the high
risk category patients, the tough nuts to crack so to speak,
to my mind it will be a safe bet that they would work that
much better with good prognosis patients. When our worst-off
members win, that is when we are all likely to win, big
time.
I regret I am
not at liberty to tell you the identity of the specific
immunotherapeutic agent(s) and chemopreventives that will be
used in this project, at this point in time. If you are
willing to take my word for it, I can tell you I am very
pleased with the choices, and optimistic that we will see
good efficacy of this combination for CLL patients.
The second
project is an effort to develop a method for screening new
drug candidates and identify those that have high
probability of success in CLL. Drug testing outside the body
whether it be in test tubes or mice has not been a
satisfactory predictor of performance in real patients. This
is because the micro-environment within our bodies is so
critical to CLL cell survival that they do not live very
long in laboratory test tubes, not long enough to carry out
meaningful drug testing. Monoclonal antibodies also serve to
increase the complexity of the problem, their mode of action
is so different compared to more conventional chemotherapy
drugs. Lack of an effective drug screening method has added
years and millions of dollars to getting new drugs to the
market place. It has also meant that it is hard to tell
ahead of time how an individual patient is going to respond
to any given therapy, without actually going through the
therapy.
The Mayo team
has developed a laboratory microenvironment where CLL cells
survive a lot longer, by doing a better job of mimicking
in-vivo conditions. If successful, it would be of great
practical value in speeding up drug testing, identifying
effective new drugs, and customizing therapy choices to suit
individual patients. In the best of all possible worlds, we
will not be shooting blind any more - we would,
instead, be able to make therapy choices based on an
understanding of how a particular drug is likely to work in
each special situation.
As you can see,
both projects have common themes. Both are pragmatic, with
emphasis on reducing toxicity to patients, use of modern
prognostic testing, emphasis on short-circuiting
developmental delays as far as possible and, hopefully, both
projects will give us practical value for our hard earned
money. I could not be happier with our choice of projects to
sponsor and fund, our choice of Dr. Kay and his team as
investigators and our collaboration with the world famous
Mayo Clinic.
This is a
special moment in the short history of CLL Topics and I am
delighted to share it with you. We embarked on this
adventure because so many of you wrote and supported this
novel concept of patients becoming more proactive in
clinical trials. Now we need you to add muscle to that
support. We hope you will be generous in the donation of
your time, your money and your fund-raising efforts.
Together we can make Project Alpha one for the history
books.
Chaya Venkat
Founder, CLL Topics
CLL Topics
Board Members:
 Bill
Duffy
Judy Fisher
Keith Friedlander
Sherry Gardner
Robert Morgan
Chaya Venkat
P. C. Venkat
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