PCI-32765 monotherapy Clinical Trial cycle 4

[Guest guest]

Cycle 4 ended on Oct.18, 140 days out. I remember thinking

how dark it was at the time I left my hotel to walk to the

Cancer Clinic. The sky was clouded from a child's

palate of gray brown mud-colors washed with dull orange as

if part of Columbus may have been burning. The Dodridge

bridge St. construction completely blocked the bike/hike

path necessitating a bit of trespassing up a bank and

through a student housing property to regain the path on the

other side. My walk allows priority questions to percolate

to the surface and I decide to push the issue of seeing Dr.

Byrd to try and get a handle on what has caused the

pancytopenia during my catheter ablation hospital stay and

to talk about my chronic eye discharge/irritation. As I pass

under the Art Deco bridge on W. Lane Ave I am surprised to

pass so near to a Great Blue heron, stilt footed at the

river's edge, head scrunched between his shoulders the dour

" humbug " countenance of Scrooge, an icon of disdain for the

approaching winter, yet another reminder that this brisk

morning's walk will soon yield to much colder and

challenging walks. See Bridge: click

http://www.fceo.co.franklin.oh.us/lane_avenue_bridge_story%201.htm

At the CTU I am handed an updated Clinical Trial Consent

form with new symptoms listed and I note " Blurred Vision " -

As far as I know I am the only one so far with this symptom.

The procedure of right atrial catheter ablation appears to

have stopped the " Atrial Flutter " but not the A-fib. I had

two episodes of A-fib with mild tachycardia (fast heart

rate) less severe than prior ablation and both lasting about

8hrs. The issue of whether to receive blood thinning after

an ablation procedure and for A-fib is formulaic for the

Cardiologist but tricky for me. I already have micro-

hematuria (blood cells in urine) and my platelets have not

recovered, stalled at around 85. While that platelet count

is not considered dangerous in and of itself, a warning

paragraph in the new Consent form states that " ... the study

drug (PCI) can prevent platelets .... from clumping

normally. " These factors have pulled me in the direction of

refusing blood thinning agents such as Warfarin as a daily

prophylaxis against ischemic stroke, which if taken, could

tilt risk toward hemorrhagic stroke. Explanation of stroke

cause, go to:

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001740/

I am granted a consultation with Dr. Byrd and we discuss the

pancytopenia I experienced but causation is not clear. The

eye issue is troublesome and it is proposed that I take 2

weeks off PCI to see if the eyes respond. I floated the idea

that the cancer, prior to any TX, had been degrading my

kidney function which worsened as the tumor in the

peripheral blood (PB) increased. PCI works by severing the

bio-chemical relationship between the CLL cells and the

stromal cell layers in the lymphnodes and marrow. When PCI

blocks the signaling pathway from the BCR to the cell

nucleus, it in turn causes a migration of the congregated

cells out of the nodes and into the PB. Could the rising PB

levels of CLL cells be a causative agent of my eye problems?

My PB tumor burden had gone from around 25k WBC at Trial's

start to 95k at the peak and was now at 52k. I thought my

eyes were not as bad as they had been in the previous cycles

so I said I would prefer to wait one more cycle before

considering a pause in PCI. Ideally I would prefer to wait

until my WBC was close to high normal (around 11k), to then

assess the eye condition. This would be a better test to

tease out the role of the PB tumor verses PCI as the driver

of the eye problems.

I was very pleased at the level of concern shown by Dr. Byrd

and his willingness to work with me on a strategy to manage

the troublesome eye side effect. He agreed to let me go

through cycle 5 to see what happens. He stressed that at

OSU, his " Clinical Trials are for his patients and not the

other way around " and did I get the difference? Yes and I

felt that from our meeting.

Thoughts about side effects. I believe it is more often the

case and truer with previously treated patients that side

effects which manifest during a clinical trial are difficult

to ascribe to the experimental drug without large numbers of

people from which data can be collected. In the microcosm of

my Trial experience, my heart problems were genetically

latent and first felt as an episode of A-fib, tachycardia

and probably Atrial flutter only after my first TX from RF.

I question how much the RF TX triggered the heart to an

earlier dysfunctional state than would probably have

happened at some point in my later life if I had not had CLL

and TX? Likewise the eye problem. If I am correct to assume

that my sinuses are affecting my eyes with irritation and

discharge, how likely was it that the severe reaction to

Rituxan this March, which resulted in an acute sinus attack,

could be the underlying origin of my eye problems? PCI may

well play a role in my side effects but it is not clear how

important a role, just as it is not clear why I reacted so

badly to Rituxan after having tolerated it so well on 1st

Cycle of RF in '09. The answer is not " blowin' in the Wind "

it is sloshin' in the blood my friends. Until researchers

connect a lot more dots our Tx choices, whether " Gold

Standard " Therapies or through Clinical Trial experimental

drugs, will remain more of a crap shoot than what we think

of as science based best outcome decisions. Speaking from a

personal perspective and through direct observation of

patients on PCI, I would hazard a guess that anxiety about

side effects with Kinase inhibitors should be no more than

with standard therapies and are more likely to produce a

better result with less toxicity than Standard Therapy

Agents, at least in the short run.

Hoping this maybe of some value to the members.

WWW - OSU satisfied Lab Rat with a growing fondness for

cheese sandwiches -

[Guest guest]

Wayne,

I am sorry you're having these challenges, hope they resolve

soon. About your eyes, last year I did have a posterior

vitreal detachment, and the optometrist that I go to has a

machine called the Optomap, and he tested both my eyes.

Guess what showed up? (At the time, my WBCs were around

380,000). White cells, cll cells. They show up in the

eyes, too, and can be seen on the Optomap images. So can

the PVDs, which also cause blurriness. I wonder if that's

what's causing your blurriness. Many optometrists don't

have this technology, it's an expensive machine, but some

do. Perhaps you could locate an optometrist that has this

machine, and have him look at both your eyes. There are no

eyedrops involved at all. You simply gaze at a screen, and

a flash of light takes a computer photo of the eyes. It's a

really cool innovation. Here's more info on it:

http://www.optos.com/en-us/Patients/

Thanks for the detailed email. It surely will help lots of

cll patients start thinking about the risks/rewards of PCI.

Ellen

[Guest guest]

Wayne - a so beautifully composed e-mail deserves all the

attention it can get!

First, do remember that Dr. Furman, Dr. Byrd and others

running the PCI really do not know fully what to expect, the

drug is too new. Dr. Furman, I know, is looking for a

treatment that will turn the disease into a truly chronic

situation, where we will have nothing to worry about other

than forgetting to pop the daily pill. His goal with PCI is

not to cure CLL but make it into a mild " diabetes " with

which you can go on until you get hit by a truck at 95. My

conclusion: anything is possible at this point of our state

of knowledge.

The second thing I wanted to mention is the a-fibs. I've

always had them, but since my lung surgery I had them

frequently, plus something called atrial paroxysmal

fibrilations where you're racing at 150 for two minutes and

then slow down to 40. This I found very upsetting!!!!! The

explanation, believe it or not, was that the surgeon had to

move the heart around during surgery.

Now I'm doing very nicely with Metropolol 25mg in the

evening, and Digoxin 0.125mg in the morning. Hardly any

events.

Best,

[Guest guest]

Dear Wayne,

Your post reminds me about a major issue we all face in and

out of trials: how to reconcile our doctors' [areas of]

ignorance and mistakes with our certainty about and faith in

their ability. My experience in a trial made it clear to me

that as long as the doctor is willing to be open about

what's happening and answer my questions fully (even when

the answer is some version of " I don't know, but... " ) I

can then have a basis for measuring my own willingness to

continue. You already know that Dr. Byrd is an outstanding

CLL researcher and he's reassured you that you, not the

trial, come first. But it's also vital that you be candid

and clear about your level of physical discomfort, your

hesitations, your fears. Then it's up to Dr. Byrd to re-

assess the parameters of the trial requirements and see what

can be done within them.

Stopping the trial for a brief period seems like the most

logical way to approach an unknown like the blurriness;

taking a break should be a fundamental " built-in " to almost

any trial, I think, since these kinds of complications can

and will occur.

You show such courage in your approach to all this. If

you're wincing when I say it, please understand that to me

courage is all about how we manage our fear, not getting rid

of it. You are " modeling " what a trial is all about with

enormous grace for us. I know what we're all wishing that

you do well and that this problem is quickly resolved.

-Frances F.

[Guest guest]

Hi ,

Your comments are most generous. I am not sure how some of

my reporting will be viewed by members in light of my side

effects which are probably not common to the majority of our

community. I am quite sure that the anxiety that accompanies

patients during anticipation for 1st TX and entering

Clinical Trials is a common thread that connects us all. The

UNKNOWN of what to expect from just having CLL with its

myriad of potential complications and progression to say

nothing about TX response is the real source of anxiety.

Being in a situation, no matter how dire, where little in

the way of choices are offered and fast action is required

offers little time for the mind to squirm. CLL is a dance

with a " Bear " where the Bear calls the tempo and the dance

only stops when the Bear quits.

It is hoped that the portions of my posts dealing with my

eye problem and heart issues do not overshadow the relief

from the " tempo of the Bear " that I have experienced by

being on PCI. When my eyes are clear and I am not actually

in A-fib I feel like I do not have CLL (the first time since

2006). Coping with CLL and feeling free from its grip are

not qualitatively the same. This is mostly good quality

time. It is also hoped that I do not come across as winey

about my side effects as I am humbled by the battles that

others have fought and are fighting on a daily basis such as

yourself. I have learned much from how others approach their

individual problems and what they have learned in the

process. This is a much appreciated forum, thanks to you and

all who share.

Thanks , for the info on meds for your A-fib. I am

unfamiliar with Digoxin and will run it by my Cardio Doc.

WWW

[Guest guest]

Dear Group,

This may not be the kind of " facts " we like to discuss in

this group but I do think trials are very important with

regard to our disease as research continues to look for new

approaches to treating CLL. In my last post I used the

words " ignorance " and " doctor " in the same sentence; I don't

think I was very clear. I was referring to the absolutely

normal fact that in any trial, many things cannot be

predicted and there are questions that won't have easy

answers. I was fortunate to have a doctor who wasn't

reluctant to be open about what he didn't know or couldn't

predict, which bolstered my confidence in him and in the

trial. I think too often we expect our doctors to be more

than human. Seeing any doctor's limitations clearly and

then deciding if they are negatively impacting on your work

together or not is part of the challenge of being a patient.

I continue to learn from that challenge. Doctors must do

the same thing in dealing with their patients' limitations, no?

F.F.

[Guest guest]

Hi Frances,

Regarding your Nov. 7 post in which you attributed " courage "

to my journey I am afraid in all honesty I cannot retract my

" wince " . Given my ride to the edge of the abyss by the

conventional tried and true therapy agents Rituxan and

Fludarabine it was more pure cowardice on my part to agree

to participate in the PCI Clinical Trial than to face more

of the same:-) Given the unknowns of all conventional

treatment options at the time, my effort to understand how

kinase inhibitors worked and the consultation I had with Dr.

Byrd it was not that difficult a decision. I would not have

stepped up to the plate of a phase I Clinical Trial if I

could have followed the path of Malcolm Airst who went

10years on Rituxan monotherapy.

I do think your remarks on doctor ignorance was spot on. Far

too many patients are not advantaged to have access to a CLL

knowledgeable Dr. There is no shame in ignorance and

particularly when it is applied to the setting of a Clinical

Trial. Researchers can only predict so much from petri

dishes and animal models when testing new compounds in

humans. There is applicable shame applied to a medical

system that does not allow doctors the time to know what is

occurring in a patient's progression through medical care.

Because of where I live I have tried a compromise by using a

CLL expert and a more local Heme/Onc. Due to the turnover of

oncologists at one local clinic I went to I saw, too often,

what I termed Pharmacists masquerading as Doctors. From the

pressures brought to bear on Docs to cram in as many

patients as possible so the hospitals can turn a profit the

patient needs to be wary. Patients need to have the courage

to confront the health facility that employs a " dispenser of

medicines " in the place of an individual with a title of

Doctor who knows something of how to use the medicines at

their disposal to heal. My own failure at courage to refuse

a second cycle of RF in 2009 when I perceived a problem with

my kidney function nearly cost me my life and the result was

permanently damaged kidneys. That won't happen again and I

consider myself lucky to have the marginal kidney function

recovery that I do.

In any case, Thanks for the encouragement and good wishes.

WWW

[Guest guest]

Wayne,

What lead you to suspect that you had a problem brewing with

your kidneys when you were on RF?

I had RF nine years ago and didn't feel any duress during

that period of time which covered six cycles.

I now, nine years later and knowing a little more but

certainly not enough have gone through five cycles of Chemo.

Firstly Treanda which I had a very bad rash from head to toe

and was change to FCR for the an additional four cycles.

I am battling Hemolytic Anemia now. Just received three

pints of blood and am at 10.1 HGB from 6.4. I was down to

7.5 HGB and received two pints of blood before starting

Chemo this second time. I will be getting my CBC often,

IVIG and Procrit.

I am hoping the best for all CLL people.

Joan

[Guest guest]

Hi Joan,

Before I sketch out the details of my kidney issues it might

be worth a cautionary note to all and particularly new

members that a part of the heterogeneous picture of CLL is

the potential for the cancer cells to infiltrate a variety

of tissues and organs in the body. If you think of the

lymphatic system to include the spleen, a specialized

lymphnode, and all the lymphnodes throughout the body as an

organ and the blood as a liquid tissue organ with the bone

marrow as the progenitor of both we are used to seeing these

tissues as the targeted infiltrated organs of choice for

CLL/SLL cancer cells. If monitoring any CLL website for

awhile it will become clear that the " Bear " dances to many

tunes and some patients will have focussed problems with

their livers, kidneys, skin, eyes etc. Some of the problems

are from infiltrated cells or the position of enlarged nodes

pressing on organs. Some problems arise from bio-chemical

changes to the circulating blood flowing to these organs

from complex reasons too numerous to mention here. All this

aside from when we are treated with toxic compounds that add

to the complexity and variety of the pathogenic course of

CLL that adds more stress and damage to tissues and organs.

Venkat's CLLTopics was my earliest " go to CLL School " .

I began learning to read blood lab reports by first charting

a friends 4yr battle with the Bear before he got a

successful HSCT (Hematopoietic Stem Cell Transplant). After

the above paragraph of doom I owe it to you all to know that

he is 5yrs since HSCT with perfect blood work and very

minimal GVHD (Graft vs Host Disease). I began by downloading

's " Your Charts " and keeping my own color coded record

for both CBC and Comprehensive Metabolic or Electrolyte

values as my CLL progressed.

At Diagnosis I already had a significant tumor burden (ALC =

23.2k and multiple cervical and submandibular nodes). When

looking at renal function on the Comprehensive Metabolic

Panel you need to pay attention to: 1)Creatinine, 2)BUN

(Blood Urea Nitrogen) and 3)GFR (Glomerular Filtration

Rate). My creatinine was at 1.0 (Ref range .5 - 1.5) GFR was

>80 (mild kidney damage between 60 - 89, the higher the

number the better) & BUN = 24, Ref range 9-20, this was

elevated but BUN can vary greatly based on hydration alone.

Caution: do not try and compare my numbers with yours as

laboratories are different with values & reference ranges

varying from test to test.

9 months after DX the first red flag was seen when my GFR

dropped to 54, Creatinine was at 1.2. I brought this to the

attention of my PCP and he voiced some concern and ordered

an Ultra Sound to see if a node might be pressing on a

ureter. While negative for that, I learned through him (not

my local Onc at the time who wanted a CT) that the contrast

with CT scans can damage kidneys. During 34 months from DX

to 1st TX it became clear to me that there was a " saw-tooth "

progression of kidney dysfunction, a TREND culminating in

the only recorded creatinine level above normal Ref range

(1.6) which was part of my decision to end W & W. Because of

high WBC 300k+ and bulky nodes I was treated at the

Clinic at OSU. Monitoring there was very diligent and I

believe I surprised everyone by getting through the 1st

cycle with no problems. No sign of TLS (Tumor Lysis

Syndrome), No shake and Bake from R. Creatinine remained 1.3

- 1.4 and any expectation of problems from the TX would

largely diminish after 14days post week's TX. After 14days

my creatinine began drifting upward and the GFR headed down.

It was my now regrettable option, worked out ahead of time

with Heme/Onc in NY to take over the remaining cycles of TX

due to the long drive to OSU.

I was to meet with the Heme/Onc on the 1st day of my 2nd

cycle prior to infusion. I had been sending all lab work to

the Onc and charting my own CBC and Electrolyte Panel. I was

quite concerned to see that my Creatinine was at 1.8 with

the GFR at 40 and uric acid @6.5 going into the infusion. It

is recommended that Fludarabine not be given at full dosing

strength when GFR is below 60. The Onc was attending some

emergency and when I expressed my concern to the infusion

nurse she patted me reassuringly on my shoulder saying that

the doctor was aware of my blood work and I would be given

extra saline and above all not to worry because I was in

good hands. My mistake - At this point I should have at

least waited to see the Onc. Better than that, I should have

called in a nephrologist prior to this 2nd cycle.

The first day I reacted with Shake-n-Bake, 2nd day I had a

fever and I felt sick which persisted to the end of the

week. That weekend my kidneys began to shut down. During

this week of infusion I had only one blood lab to check for

infection following the fever. At the 6th day following the

last infusion my GFR = 22, creatinine peaked @ 3.1 and uric

acid was 8. Uric acid level though high, did not qualify for

TLS although lysed cell debris obviously contributed to the

already stressed kidneys resulting in ATN (Acute Tubular

Necrosis)

Kidneys are complex organs warranting a specialist medical

field and with CLL you can have a number of causes for

pathology affecting them. When I went back to the hospital

in an emergency mode the Onc plus Fellow were in panic mode

trying to figure out what to do to save my kidney function

from further damage. I demanded a Nephrologist see me and

could tell from the looks exchanged that the kidney Doc was

not happy with the saline being given to me at that time.

When one's kidneys are undergoing tubular necrosis it

affects your blood pressure and electrolytes can rapidly

become imbalanced. My potassium shot up threatening my heart

etc.

The lessons to take from my little adventure with kidney

failure is: monitor your own blood labs and if you see a

TREND in values of your kidney numbers or liver numbers

heading south, raise the issue with your Onc. If you have

kidney dysfunction get a nephrologist on your team so he/she

will be familiar with what is going on with you. Also keep

in mind that things can go wrong and need monitoring well

into TX and beyond the arbitrary 14 days post 1st TX cycle

that works for most folks.

Off to OSU tommorrow for end of Cycle 5 on PCI.

WWW