FCR+L Trial

A lot has happened since my last post. I've been trying to get into the FCR+L trial since May, and I finally am supposed to start on Sunday, September 22, 2008. (There is a wrinkle; I've just developed a cough, so I need to have that checked out before I start the trial).

I was notified on Thursday that I have been randomized to be in the arm of the trial that includes the lumiliximab. Lumiliximab is a CD-23 antibody. It works in a fashion like rituximab, but the CD-23 marker isn't as good of a target.

The difference is that the CD-20 marker is a transmembrane protein; it pokes part of itself outside of the lymphocyte, and keeps the 'tail end' inside of the cell, in the cytoplasm I would assume. The way these markers work is they are the 'eyes and ears' of the cell, sensory organs if you will. The marker detects a signal outside of the cell in the microenvironment, and then signals inside of the cell.

Being a transmembrane molecule, the CD-2o marker is a robust one, hanging on the the cell (in large numbers, in the thousands), resisting falling off and becoming useless. The CD-23 marker, unlike the CD-20, is much more easily dislodged from the cell, and a detectable fraction of the markers are found in the microenvironment. This makes the CD-23 marker less effective at killing CLL cells.

The hope the company who is pushing this MoAB through clinical trials is that it will enhance standard therapies. Small studies have suggested that this is true; the complete remission rate with FCR+L is higher than plain old FCR.

I am scheduled to start the study this coming week at the University of California, Davis Medical Center. Although I've gotten all of my treatment so far from UC San Diego, I opted for UCD this time because the trial protocol they offered me allowed either MRIs or CT scans. Anyone who knows me knows that I dislike CT scans because of the amount of radiation, which raises the risk of secondary malignancies, a complication CLL patients are already at higher risk for.

The secondary reason is that I live in Sacramento, and this will mean not having to fly down to San Diego for follow-up visits and all six cycles, assuming I would get that far.

As far as my general health goes, I am fading, but not at a fast clip. My biggest problem is my anemia. I am in the 8.8 range at last test, and this is not normal. Even the government will pay for Epogen if the hemo rate is below 10.0, which I am.

My other numbers are terrible, but sort of holding steady. WBC at the 200,000 range, platelets (always a problem for me) at about 75, and the red blood counts, as I've mentioned, a continuing problem.

My latest test should be on my fax machine when I get home tonight, so I should know if I need a transfusion in the next day or two.

My biggest problem right now is this cough I can't get rid of. Dr. Hamblin believes I should wait before I start the trial, and I am inclined to agree with him.

I think I got this latest infection (I've been remarkably infection-free even with terrible numbers, until this year, and I've had three infections since January) from using a neti pot. This is a device that allows you to pour salt water from one nostril into the other, draining stuff and supposedly keeping you clean. However, I made the mistake of just using tap water, which is not sterile. I usually boil the water, but just forgot.

This cough has now settled into my chest. Well will see what happens.

Still Waiting

I'm waiting for approval of my MRI imaging studies before I can enter the FCR+lumiliximab trial at UC Davis. The trial coordinator is Dr. Tuscano, who was nice enough to speak before the Sacramento CLL patient's group in 2006. He has been working on his own antibody, but I've not heard whether anything will come of it. It looks to be a less than rousing success, but the delays may be due to funding or other administrative problem.

So I'm in a holding pattern, in more ways than one.

One development is that I'm going down to UCSD to see either Dr. Kipps or Dr. Castro. We will see what is happening with my run-away CLL. I am less than happy with the skyrocketing counts that are not, so far, really apparent except in my large abdominal nodes. I don't feel any changes, still working full time and in the evenings seven days a week. Haven't been back in the mountains since I'm now anemic and I don't want to give myself a heart attack by hiking. Energy level has been dropping, but I'm sleeping fairly normally.

Lumiliximab is a CD23 antibody. CD23 is not expected to be a slam-bang MoAB like rituximab for the simple reason it doesn't seem to has as much killing power.

The most recent study and the reason I think Dr. Kipps has recommended this study to me is that the complete remission rate is almost 50% in previously treated patients, which is a very good result. Overall response rate is 95%.

There are two arms to the study, and you don't know what you are getting into before you sign up. You do know once the treatment is underway, so I will get at least one FCR course if I am accepted into the trial. I have more negatives (low platelets, etc.) than I did before trial number one and two. The more things wrong you have with you, the less likely they will choose you to be in their sample. They do want a success, and some folks have been accused of 'cherry-picking' patients that they think will do well for a particular trial.

It's such a game; a game with deadly consequences for the patient, at least.

I saw an oncologist at UC Davis regarding the FCR+Lumiliximab trial (a word she cannot pronounce accurately). This is the same trial which was offered (recommended?) to me by Dr. Kipps. However, Dr. Hamblin calls this trial just a 'marketing scheme,' a phrase that I don't understand. I'll have to write him and ask him to explain.

I don't want to use fludarabine, of course, since it is linked to significant T cell suppression, secondary malignancies, premature death and a whole host of other problems. Once you are refractory to fludarabine (and you will become refractory), then they are no real options left for you; make sure your affairs are in order!

I was more interested in the lumiliximab trial (which is a randomized phase II trial, somewhat rare) as offered by UCD over that of UCSD, since the trial at UCD offers the option of MRIs instead of CT scans. Funny that the same company would have different protocols for different institutions. I did e-mail the company complaining that MRIs would be just as effective as CT scans at tracking the disease. The company MD who replied to me said it would be up to the trial administrator. However, the written protocol is different for the two institutions.

I'll keep this blog posted as to what happens.

CLL Rampaging Out of Control!

Since my last post, all hell has broken loose, and my CLL is out of control.

My last blood test on June 19 had my WBC declining by 20k or so. I expected at least only a modest rise, if any, based on how I felt.

Wrong!

My numbers have gone sky-high, from about 30k to over 176k, in one month. I guess this qualifies as doubling in less than six months.

Thank goodness for blood tests, because I wouldn't have known I was going downhill so fast without them.

We've decided to treat as soon as possible, with something. We've decided that I should get a blood retest this week. I've been putting it off because, well, ignorance is bliss??? Isn't it???

With all the new knowledge and the prospects of better treatments in the next few years, why is this going so quickly downhill for me? That's just the way it is.

If CLL has taught me anything, it has taught me that we are all dying, some of us have it thrust in our faces every day, others only know it as an abstract thing. I used to confront this like the rest of the world, as a distant possibility; not now.

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We don't know if it's Richter's transformation, rapidly progressing CLL, a new cancer, or something else.

My only 'B' symptoms is that I'm tiring a bit earlier than I was a few weeks/months ago.

I'm not buying extra supplies that I might need 'someday'. That's a waste of money.

Vacation from CLL

I last saw Dr. Kipps on June 19, 2008. I cancelled the July 3 appointment with Dr. Castro because it relates to the ISG-35 internode injection trial which I failed in late May. (I went from 30k to 60k in three weeks. Bummer.)

I've had several major issues with my wife. She has asthma and the hot and smoky weather in Sacramento (we always have very hot Julys, but not smoky ones) has affected her in a major way. I've shifted my focus from my CLL to her asthma.

So, the last week, I've been feeling so good I decided to cancel the July 24 appointment with Dr. Castro (also on the failed clinical trial. I thought blood work here in Sacramento would give them a picture of what is going on with me, without having to fly down to San Diego, and spending the full day down there. I hate that!

I decided I would take a slight vacation from my CLL, in a way. I thought I would take the last week and one-half, and just not think about my CLL or any other medical problems.

I got a blood draw on Monday. I'm hoping the WBC is still low, and all of the other numbers continue to be stable.

I went for a hike on Sunday and did extremely well, felt fine, and thought about doing a long hike in September or so, if I can get in appropriate condition. I was worried about anemia as I had a night of blood pounding in my ear (see Dave's blog; he found it was associated with autoimmune hemolytic anemia), but I did fine and felt wonderful. I don't think I have significant anemia, if I have any at all.

It is nice to not have to think about CLL for a week and a half.

Takin' a break

I'm obviously informal since I am using an apostrophe instead of a 'g' in taking!

The weather has vastly improved. Last week was what Sacramento is famous for, hot weather! And it was hot, hot, hot! We topped out at 109 or 110, depending on where in the Sacramento region you are.

I bought a window air conditioner for the laundry room, for our semi-feral cat Mrs. Chippy. It was so terribly hot in the garage (the laundry room is the breezeway, sort of, between the garage and the house. It worked great! For $62, it was a bargain and it lowered the temperature into the 80s, a big relief from the 110 degrees it was probably in the garage. I'm going to keep the A/C there until summer is over in two months, and then put it away until next year.

On the topic: I've decided to take a break from CLL. I know that sounds odd, but I've had treatment in September, October and November 2006, and then again in May, '08. I had a partial remission from the HDMP+HDR (high dose rituximab), but relapsed quickly. I have terrible markers and no one, including me, was expecting me to last 10 years with this form of CLL. (It will be 10 years on October 1.)

My last blood numbers on June 19 showed a nice drop from my rapidly escalating WBC, and I feel pretty good, so, why not? I did see the local oncologist at UC Davis regarding the lumiliximab (randomized to 1/2 of the participants) trial. They remarked that they thought it was odd I'd be undergoing treatment when my performance level is '0' (zero, the lower number the better), working full-time, etc. So I took that as sort of a sign, maybe from God, to ignore the disease for a month. I'll have my next blood test on July 19, which is coming up fast. We will decide what to do then.

In the meantime, I am chugging away. My wife, who has severe asthma, is having trouble with our high temperatures and smoky conditions. Visibilities have been on the order of a mile or so. Terrible. You can see the smoke in the air, the sun 'sets' about 4 pm, and there is actually ash falling nearby. It has been a horrible year.

Note the sad loss of P.C., Chaya's husband, Tony Snow and others from cancer. This disease seems to take the best and the brightest, doesn't it? I don't have survivor's guilt, because I will most likely die from CLL unless something else gets me first, and it could happen in a hour, a day, or a week from now.

So, a short break from researching CLL, reading CLL blogs, thinking about the physiological nature of the disease, etc., is in order for me, and, I might add, richly deserved, at least in my opinion!

The Ups and Downs of Gene Therapy

I saw Dr. Kipps on June 19, 2008. I had an excellent week the week of June 7th. I had lots of energy and got a lot done. Not quite as good this past week, but not bad.

My WBC has unexpectedly taken a turn down, which of course is good. I don't have the exact numbers, but they were up around 60,000, and have now dropped down to the 30,000 range. This is a pretty good drop. Dr. Kipps says that isn't unexpected after the gene therapy, and even after the counts have gone up the past three weeks.

To re-cap, I had the ISF35, inter-nodal injection on May 5th. I was very sick, but recovered fairly well after a couple of days, though I waited until May 12 to go back to work to be on the safe side. My counts dropped very nicely the next two weeks, but started heading upwards the third week, so I was off the trial (though there were no other treatments scheduled anyway, since this was a one-shot deal). The next appointment in early June saw my counts go up even higher. So, we started talking about FCR or FCR+lumiliximab (CD23 antibody). However, by June 19th, the counts dropped. So, there may have been a somewhat delayed action of my immune system? No one knows.

I found out that there is a FCR+L trial in Sacramento at UC Davis, through Dr. Tuscano. It would certainly be much nicer not to have to travel to San Diego and spend the money on flights and hotel rooms, instead staying here in SacTown. I did have an appointment with UC Davis on Monday, June 23 to check into the trial. I'm not sure exactly what to do right now.

I'm thinking of having another CBC (complete blood count) to see where my WBC are now. I must say that my nodes in my abdomen aren't shrinking, and this is an area of proliferation. I suppose a bone marrow biopsy would be a good idea to see what is going on as well. The danger is waiting too long for treatment; the danger is also treating if another treatment is still working, and doing something that isn't necessary right now.

However, Drs. Kipps, Castro and Weirda all think FCR or FCR+L are probably a good idea right now.

And then there is the problem with the huge radiation dose from multiple CT scans; of the neck, thorax, and abdomen. It is about 500 times the background radiation. Of course, with my probably limited lifespan, it may be that I just won't have time for a new cancer to begin. However, it still is of concern to me, if for no other reason than an MRI would be just as good.

So, we are in limbo now.

On a personal note, I noticed one of our dogs had a cyst-like lump on his side that was bleeding. This was on Thursday. We arranged for surgery yesterday, Friday. Sparky is out of surgery and doing well this Saturday. If he holds, we will bring him home tonight. Poor guy is an older gentleman of about 15. He is a funny dog who loves to be with the family.

A hot day in Sacramento, and I'm cranky

I get cranky and out-of-sorts when it gets above 100. The A/C is out at work (they swear it is working (sigh) but I've attached a thin piece of paper to the vent, and this paper moves like crazy when air is coming out. The paper is dead, not moving. There is no A/C) so I've been hot all day. I got a lot of work done today, but once I got to the shop this evening, working out in the garage, it's been terrible.

I go to San Diego to see Kipps tomorrow. He's been out of town doing the presentation and hob-knobbing bit again, so he is doubling up on clinic days. I'm sure he is tired from his trip and seeing so many patients. His patient load is growing more and more, I think.

For the first time, I'm worried about my treatment. I've failed two treatments so far, and the FCR plus lumiliximab just seems dangerous to me. This is real chemo with nasty drugs that cause mutations in normal and CLL cells.

I don't have anything to base this on, but I'm usually accurate in my prognostic dreams and feelings. I'm not happy about feeling worried. But I suppose I have to do something for my growing CLL problem, and they don't have anything good to offer me. We are down to the second and third tier drugs that have major side effects.

And, Dr. Castro two weeks ago said I should be thinking of moving to a transplant. Dr. Weirda just about promised me three years of remission with FCR, but obviously UCSD doesn't think I'll last that long.

Worrisome. But we all die sometime. I'm having that lesson drummed into me like there is no tomorrow (bad choice of words?).

What Will Be My Next Step?

We are weighing the merits of my next treatment. I've failed two so far, meaning my CLL cells are quite resistant to treatment.

My plan at the beginning was to use less toxic treatments with the idea that this would preserve my immune system as long as possible, and save the more powerful treatments for when I needed them. The downside to this approach is that mild treatments won't give a long remission, and meanwhile the clone is more and more unstable, leading to a complex karyotype, meaning a mixture of more and more chromosomal abnormalities, i.e. 6q del, 11q del and perhaps a mixture of even more abnormalitites.

This can make treatment more difficult.

The positive news is that I have not had any more real problems, I continue to work, I've not come down with any additional infections, and I've gotten permission at work to move to a more isolated part of the building, where I will come into contact with fewer sick people. This is one strategy I am attempting to prolong a healthy life.

I have an appointment June 6th to consider my next move. Dr. Kipps says he does not want me to get into an emergency situation with my growing abdominal nodes, perhaps requiring intervention here in Sacramento.

An update

I've been getting slightly worse as time goes on :(

I finally succeeded in getting into the Ad-ISF35 gene therapy trial offered through UC San Diego. Dr. Castro is the principal investigator.

I had a rough time of it during the aftermath of the injection process. I had significant chills and vomited three times during the night and the next morning. I would recommend not eating lunch and dinner the day of the injection. According to staff, you will be sick.

My results were good for about a week! Two weeks after the trial, I noticed all of my nodes were down about 1/2, and my terrible abdominal nodes seemed to be smaller, to the point I was actually thinking of going back down a couple of waist sizes.

Unfortunately, that was not to last. At this point, three weeks after my trials and tribulations, my nodes have returned to pre-treatment levels, and I've grown a new, large node at the mid-line of my abdomen. This is proving to be very painful and troublesome. I am worried at this point about abdominal obstruction. I've been taking medication to make sure I don't get constipated.

At this point, I'm not sure what I will be doing. I am a bit worried about Richter's transformation. It is more common in patients with 11q del (me), large abdominal nodes (me) and increases with length of time with CLL (me).

I am trying a heating pad morning and evening to try to 'soften' the lymph nodes. Maybe it is helping as I don't feel quite as bad today.