Changing names, ownerships
Just when you were getting used to CAL-101, it is time to re-file this drug under a new acronym. Calistoga Pharmaceutical has been bought out, lock stock and barrel, by Gilead Sciences. Rumor has it CAL-101 was considered one of the crown jewels. With new ownership comes the new name, GS-1101. No doubt they will have a much more sexy brand name once the drug gets FDA approval and available commercially. In the meantime, don’t get confused by this proliferation of drug titles. CAL-101 is the same exact thing as GS-1101.
Below is my review of the design of their latest clinical trial. Results of the trial itself will not be available for many moons. This article reviews the design of the trial, because I think there are a couple of details here that may trip up patient recruitment. Earlier on, I had several serious concerns about the trial design and my review would have been quite a bit more negative. Fortunately, the company was willing to discuss my concerns in a detailed phone conversation. It is a little bit complicated and you really need to understand your options before you sign up, but now I believe this trial is worth considering if you fit the inclusion criteria and you are looking to participate in this kinase inhibitor trial.
Trial Design
You can read the official description of the trial by clicking on the link to the clinicaltrials.gov citation. I strongly urge you to read it. It has inclusion criteria, contact information etc. Right now they are recruiting at four centers in the USA, including the prestigious Long Island Jewish Hospital.
Basically, they want to recruit 160 patients. These guys will be randomly assigned to either of two arms, 80 in each arm. One arm will get 8 infusions of Rituxan over a 24 week period, along with 150mg of CAL-101 pill, to be taken twice daily. The other arm will be the control arm. These guys will get the 8 infusions of Rituxan too, but instead of CAL-101 pills they will get placebo pills for the duration of the 24 weeks. So, it boils down to comparing CAL101 + Rituxan versus Rituxan alone.
As you can see below, the study wants to recruit pretty advanced CLL patients.
- You must have been previously treated for CLL. In other words, they do not want chemo virgins.
- You must fit the criteria for needing therapy to control the CLL now.
- They are looking to recruit patients whose disease is aggressive enough that they got only a short remission (less than 2 years) from their previous round of therapy.
- Patients must have other health problems (co-morbidities) or sufficient bone marrow damage from prior therapies that they are not considered fit to undergo additional chemoimmunotherapy.
- Patients should not be refractory to Rituxan. (I wonder how they determine that?)
I will be the first to admit, this is going to be a pretty tough crowd. That makes the trial design all the more important – as I attempt to explain below.
Late stage patients such as these guys do not have time to waste, their window of opportunity is rather limited and they need to be smart in their therapy choices.
The experimental arm (which uses CAL-101 + Rituxan) makes lots of sense. As we have seen before, CAL-101 has the ability to flush CLL cells out of their comfortable and safe niches in the lymph nodes, where they are hard to reach and even harder to kill. Patients treated with CAL-101 in earlier studies have seen remarkable and rapid shrinking of their swollen lymph nodes. Of course, all those CLL cells driven out of the lymph nodes have to go somewhere and that somewhere is blood circulation. A spike in peripheral blood lymphocyte counts (WBC, ALC) have been observed upon treatment with CAL-101. This is not something that should freak you out. It is not only expected, it is to be desired. CLL cells out in open blood circulation are a lot more vulnerable and easier to kill. Combining CAL-101 with Rituxan may give us the capability of (1) flushing out the CLL cells out of lymph nodes (2) killing them dead once they are out in the open. This one-two punch is what makes this combination so interesting. Incidentally, the new generation of kinase inhibitors such as CAL-101 and PCI-32765 do not seem to care about prognostic indicators. In other words, even guys with poor prognostic indicators – including the dreaded 17p deletion – seem to respond nicely.
But since this is a two arm, randomized study, you do not have any guarantee that you will indeed end up in the CAL-101 + Rituxan arm. You have a 50:50 chance of being placed in the control arm. Patients in the control arm will get 8 infusions of Rituxan over a period of 24 weeks (6 months). The trial is also supposed to be “blind”, in the sense that the control arm folks will also get pills to swallow each day but in their case the pills are bogus – placebo pills. I doubt the “blind” part of the trial will work out quite that way; I expect most patients will be able to tell whether or not they are getting CAL-101, based on how their nodes (and blood counts) behave. No shrinking of the nodes, no increase in blood lymphocyte counts means you are probably in the control arm.
I am willing to bet most patients will volunteer for this trial because they hope to be in the experimental arm. It pays to be realistic. Exactly half of you will be in the control arm. As I discuss below in the editorial section, that poses some risks and questions.
As a single agent, Rituxan is not all that effective even under the best of circumstances (chemo naive and good prognosis patients) and it is not likely to do a whole heck of a lot for this crowd. So, my concern prior to discussions with the company was simply this: are the folks in the control arm being sacrificed with less than optimum treatment just so they serve as a reference point? If that had been the case, I would have had real problems with this trial. Why would anyone in the control arm hang around for 24 weeks if they experience disease progression while being treated with single agent Rituxan? I hope you know by now, patients have an absolute right to walk out of any clinical trial, vote with their feet as it were. I had visions of the researchers retaining most of their 80 patients in the experimental arm, while a large percentage of the control group dropped out of the trial.
As it turns out, there is an important loophole to finessing this dilemma. The company is also initiating a follow-on trial, an extension of this trial. Here is the citation link to the extension trial. Anyone in the original trial who is tolerating therapy but whose CLL progresses while being treated can switch over to this extension trial. This too is a two arm trial, but everyone in it gets CAL-101. The difference is that some of the patients will get the “standard” dose of 150mg twice daily, while others will get a heftier 300 mg twice daily. In other words, the safety net for the control group folks is that if your CLL progresses while you are on single agent Rituxan, you can switch over to the extension trial and get put on CAL-101, without having to wait to complete the 8 infusions and the 24 week period. Phew. You can see why this is an important detail.
I have no doubt the results of this large scale and double arm trial will be of great importance in future FDA approval considerations. If you decide to volunteer for this trial, my heartfelt thanks. Your generosity and courage will pave the way for development of this and other kinase inhibitor drugs for other CLL patients. But I want you to remember this: informed consent means just that, your consent, after you are fully informed. We do not yet know all the pros and cons of this new drug. That is the whole point of doing this study, to learn more about it. But there are other details that do impact your risk exposure and these are things you should know about. Volunteering without knowing what you are signing up for is a sucker’s game. You may want to browse through my earlier articles on CAL-101 for additional details about this drug. Much of the commentary below that I would like you to consider is my own layperson opinion. As such, it is best presented under the editorial section. I try hard to distinguish between official details and my own opinions, but sometimes the distinction is hard to make.
Editorial
“Straw-man comparisons” are all the rage these days. Earlier, we wrote about another company getting FDA approval by comparing bendamustine against less-than-robust dose of chlorambucil. Campath approvals in this country also involved similar shenanigans. What is the surest way of making your particular drug look better? Compare it against a drug / dosage that is very likely to be a loser. I have this girl friend who loves to be photographed standing next to me – the contrast makes her look so much slimmer and prettier.
The best chance of getting halfway decent remission statistics (overall response rate and percentage of CR remissions) with single agent Rituxan is if the patient is chemo naive and the prognostic factors are pointing to a less aggressive disease. That is definitely not the profile of this patient group. So, what are the chances that majority of the control arm will get decent responses using Rituxan only? Slim, in my opinion. Increasing the dose of Rituxan or giving 8 infusions of it rather than the standard 4 infusions is not going to make a huge difference. The company argues otherwise, but I am willing to bet dollars to donuts that the results of this trial will prove me right to be skeptical about it.
Is this trial yet another straw-man comparison? In my layperson opinion, yes. If you were trot out these 160 patients before one of our highly regarded CLL experts, all of them with multiple layers of chemotherapy in their past and relatively aggressive disease to boot (as proven by less than two year remission the last time around), co-morbidities and possibly damaged bone marrow, I am willing to bet the expert would not consider single agent Rituxan as the best therapy choice for many of them. Heavy-duty chemotherapy is contra-indicated for these folks, but here are some other options that may be more interesting.
- If all we are looking for was more or less palliative therapy for these guys, an oral pill such as chlorambucil would be the choice. The poor dears are not bothered with all the nasty intravenous infusions, they will get some symptomatic relief and that will be that. What can you expect, patient had aggressive cancer and a lot of other medical problems as well. RIP, nothing to see here folks, move on please.
- If we are inclined to be a bit more creative and think a bit outside the box, we might consider Revlimid as the therapy choice. It too is a pill, taken orally. Taken at low doses it is relatively easy to tolerate. And unlike either chlorambucil or Rituxan, it is thought to increase immunoglobulin levels, something that might help general level of immunity in this rather frail group of patients. Remember, these guys were specially recruited for having health problems in addition to late stage CLL, and many of them also had bone marrow damage from prior therapies – resulting in anemia, neutropenia etc. It might be good to get some of the immune modulating effects of Revlimid.
- Yet another choice may be ofatumumab, since there is some evidence (not totally compelling evidence, but hey, we will take every ray of hope) that it works better than Rituxan.
- There are other single arm clinical trials with experimental drugs that may be worth considering. GA-101, a third generation anti-CD20 monoclonal antibody similar to Rituxan and ofatumumab may be a good choice. ABT-263, a new BCL-2 inhibitor presently in clinical trials is another option to consider.
Patients have no choice in whether they get into the experimental arm or the control arm. That choice is made for them through computerized randomization. Since this is a 1:1 split, you have exactly 50% chance of getting into the experimental arm or the control arm. Forcing 80 patients in the control arm to cool their jets for 24 weeks with less than effective single agent Rituxan therapy would have been hard to swallow. Remember, the inclusion criteria mandated that their CLL had relapsed to the point where treatment was necessary. Marking time for 6 months with less than effective therapy would have raised some ethical flags – I hope. There is this little concept called “do no harm”. We do not want to short change patients in the control arm, just to make the experimental arm look that much better.
What makes this trial palatable is that it offers patients whose disease progresses while they are in the trial to switch over to the next trial where everyone gets CAL-101. Here is what I think will happen. A significant majority of patients in the control arm of the trial (the guys getting just Rituxan) will have progressive disease. This is baked in the cake, since Rituxan is not likely to be all that effective in this tough patient cohort. Before the 24 weeks are up, many of them would have moved to the extension trial, where everyone would have access to the kinase inhibitor CAL-101. Company gets its favorable comparison to show to the FDA, even patients in the control arm get access to CAL-101. Everyone is happy. Sort of. We live in interesting times.
Let us talk a bit about money. As many of you have found out the hard way by now, not every insurance company covers participation in clinical trials. Drug companies often cover the cost of their experimental drug, but you (or your insurance) is generally expected to cover the cost of so-called standard of care, which includes all the blood tests etc that would have been done routinely, as well as non-experimental drugs. So, my question to the company was this. Who pays for the 8 infusions of Rituxan? Many of our members have life-time caps on what their insurance companies will pay. If you get randomized into the control arm, imagine having to pay for 8 infusions of Rituxan out of pocket or having it eat into your life-time cap of insurance coverage – especially if like me you think single agent Rituxan is not your best choice at this stage of the game. Fortunately, the company told me that in situations where there are issues with insurance coverage, they will also pick up the tab for Rituxan. Please tuck this little point away someplace in your brain, it might come in handy. Somehow, I do not think anyone will volunteer to pay for your Rituxan infusions, if you don’t raise the question yourself.
CAL-101 results that we reviewed in previous articles suggests the experimental arm is not likely to be free of adverse effects. High grade pneumonia and neutropenia were seen in significant percentage of patients in previous trials using CAL-101. Prophylactic protection such as Bactrim (against bacterial pneumonia), growth factors (Neupogen or Neulasta to combat neutropenia) are recommended, but not mandated by the trial. If the local guy who is monitoring you for the duration of the trial is less than proactive, I strongly urge you to be your own best advocate. You have heard about squeaky wheels getting oiled, have you not? If you are a high risk candidate for contracting a painful case of shingles while you are on the trial, be sure to discuss this as well. While it is not a good idea for our guys to get the shingles vaccine (it has live virus in it and contra-indicated for CLL patients), you might be well served by daily dose of Acyclovir, Famvir etc.
If at any time during the course of your participation in this trial you find yourself having difficulty breathing, if your oxygen saturation level begins to fall, make sure you contact the trial researchers right away. It may not be enough to head to the ER room, since the staff there may not be aware of the special circumstances. Not all the pneumonia cases seen in kinase inhibitor trials have bacterial or viral origins, and in such cases they are not likely to be controlled by broad spectrum antibiotics or anti-virals. It the problem is due to a drug induced inflammatory cascade, the patient may need to be on large doses of prednisone to control the inflammation. This is hardly standard operating procedure for ER docs treating garden variety pneumonia. You are better off bringing it to the attention of the researchers who would know what to look for.
Another item I discussed with the company during out phone conversation was potential risk of tumor lysis syndrome, especially in the experimental group. In brief, if CLL cells are killed in huge numbers and the cell kill happens more quickly than the body’s ability to handle the debris of dying cells, there is risk of your kidneys (and other organs) getting over-loaded. This patient cohort is medically challenged group, with co-morbidities on top of CLL. If as expected CAL-101 causes a massive increase in WBC, and this in turn leads to massive CLL cell kill by co-administered Rituxan, we may have a situation where there is too much of a good thing, too many CLL cells getting killed too quickly. One of the drugs used to protect the liver where there is potential risk of toxicity is allopurinol. Rasburicase is another drug, to be used as a second line of defense. We have discussed tumor lysis syndrome and rasburicase in earlier articles. Once again, the company told me they do not mandate the use of allopurinol ahead of start of therapy. But they do not forbid it either. It is up to the local guy taking care of the patient. What if he is less than pro-active? Aha. That is where it helps if you, dear patient , know what to ask for.
This is an important clinical trial. If we want to see this new generation of kinase inhibitor drugs make it into commercial availability, we have to do our share of the heavy lifting and volunteer for such trials. If you have any other questions that you would like for me to bring to the attention of the company, let me know. I will do my best to get you their answers. Last but not least, I asked the company whether they plan to thank the patients who volunteered for this clinical trial when they write up the results for publication. I was given solemn guarantees that this would be done. Let me jump the gun a bit and thank you right now.
Site News
I had a great time meeting some of you at the CLL-PAG conference at Niagara Falls, Canada. I am also looking forward to the UK Midlands CLL conference end of this month. It will be sad visiting the UK CLL group and not seeing my friend Dr. Terry Hamblin. His death continues to be a huge loss to our patient community.
I would also like to take this opportunity to announce our first CLL workshop for 2012. It will be on Saturday, June 9th. Location, Columbia MD. As always, there is no charge for attendance. The details regarding registration for the workshop are pretty much the same as on prior occasions and you can read them here. We will be discussing some of the material I presented at the Canadian and UK conferences. More details will be forthcoming in the next week or so, I just thought I would get the date out so that people can put it in their schedules.
33 comments on "CAL-101: Phase 3 Trial in Combination With Rituxan"
Thanks so much for the information. I have been eagerly waiting for a trial such as this to get underway.
Dear Chaya –
Thank you for another outstanding article about an important CLL topic. I am currently untreated early stage W&W but as always I learn a great deal from all of your articles.
For those CLL patients who may want to consider this trial, you have provided some invaluable and easy to understand information.
Whenever I read one of your articles or visit your website I am aware of the tremendous service you provide for our entire CLL community. Thank you for all that you do to help us better understand and deal with our CLL.
Regards – Patti Kruse
PS: I hope your new puppy “Buddy” is doing well
Thanks Chaya – I echo Patti’s comments.
Rick
Thank you for your advocacy Chaya. It is much appreciated.
Chaya, you continue to be AMAZING !!!
I’m sorry I didn’t get to meet you while we were in Niagara Falls.
All the best,
Mal Blotner, ChE
Chaya, thank you again for keeping us informed about the latest developments and trials in the CLL world. I always appreciate your critical analysis; without it we would all be at such a disadvantage! I know, I would be lost.
I was very sorry to hear about Dr Terry Hamblin’s passing. May he rest in peace!
Chaya, this is so on point for me, as I contemplate next steps. Words can never adequately describe the value you bring to our table. I can not thank you enough.
Bob Larkin
Dear Chaya,
Thank you for a very good analysis of this new trial. I think you are on point in all of your conclusions. Very nice job.
One point regarding the design employing a control. I have heard from the team here at the James that the FDA had apparently insisted that for PCI-32765 to be approved, clinical results with controls had to be presented. This forces the dilemma of designating a control group – while attempting to do no harm. I don’t know if the situation may be (or anticipated to be) the same for Cal-101. Any more concrete information you or someone may have on this point is appreciated. The delays from additional trials prior to wider release of beneficial drugs has a toll taken in our lives – although additional trials will somewhat better define the benefits and negative effects of these new treatments.
As you may know, PCI-32765 has also been given a new name, “Ibrutinib,” by the company.
Good analysis, there seems to be a bit of Sophie’s choice here. If too many people abandon the control arm to get cal-101 in the alternate trial, their trial will be a waste of time and could cost other people the opportunity to get this possibly effective drug. On the other hand, who wants to be the person to give their life in the name of some drug company? We had the debate in ethic class, it is worth 1 life to cure cancer. I was surprised at how many people quickly sacrificed someone else’s life in the name of a cancer cure. I think the job can get done without this violation of “do no harm”.
If you are considering doing this trial and would consider a quick exit, from the last I heard clinical trials using “placebo” have to use the standard placebo pill, which is, as indicated, a sugar pill. A 3 yr old child can tell the difference between a medication and the placebo.
Best of luck to the trial and more importantly, CLL patients.
A phase III trial comparing Ibrutinib, PCI-32765, as single agent vs. Ofatumumab was posted on clinicaltrials.gov as of April 11. “Not yet recruiting.” Have not looked at the details. Might be of interest. Y
hansoncllr
Dear Chaya,
I probably fit the criteria for this trial and maybe earlier ones too. Participation has been discussed with my oncologist but in each case we have decided to pass. CLL is not a “one fits all” disease. Each of us can have different symptoms and react differently to the treatments.
I am a CLL survivor (1998) who discovered CLL Topics before all the “new cures”. Treatments have been Rituxan/Fludarabine(2004), Campath(2005)and Rituxan(2007,8,9,11) and all have kept my CLL in check.
I am lucky, my symptoms have always been only low platelets and high lymphocytes(>80%). The last few years Rituxan has been my only treatment.
Thanks, Chaya, for keeping us all updated on these trials.
Thanks as always for arming us with unbiased information so we can fight our CLL corner. I’m so glad not to have to be the one rolling the dice with this 50/50 chance.
Look forward to meeting you in person at the UK Midlands conference.
Chaya, thanks for the info. I am eagerly awaiting the outcome of this clinical trial. I have had no indication of a relapse of CLL after FCR treatment at MD Anderson three years ago but I remain on the lookout for the best option should a relapse occur.
Just a note to anyone who joins the trial, my husband is on the early CAL101 + R trial and did get quite a reaction of tumor lysis after the first R infusion + pill and ended up in the ER. I would also suggest that anyone on the new trial insist on allopurinol and keep a heads up on the first infusion date. The combo works well, and quickly. Do watch for the cough, as that is a sign of a lung issue, probably a very early sign.
A small technical matter (see your editorial)…allopurinol and rasburicase may help to protect the kidneys, not really the liver.
The utility of either drug likely would best be decided on an individual basis after assessing the enrollees prior history with therapy and current ALC status and uric acid levels. The potential for harm from allopurinol is more than negligible and the utility of rasburicase is limited by it’s very short duration of action, though it is certainly useful in patients with already high-normal to elevated uric acid levels, especially when rapid cell kill is likely.
Rituximab is sort of a ‘straw man’, but there aren’t many good alternatives at this stage.
Ofatumumab may or may not have been a better alternative, but, bear in mind that patients in the original trials which led to it’s acceptance often developed progressive disease, especially during the ‘maintenance’ phase (after the initial 8 weekly doses when doses 9 through 12 were administered every 4 weeks). As it has been used more and more, there have been increasing incidence of issues such as sensory neuropathy, etc.
In my opinion, lenalidomide would have been a poor choice because of the variability of response at low doses, the duration of treatment needed to achieve good responses, and the high incidence of adverse effects at higher doses. Toxicities of rituximab are likely easier to separate from toxicities of GS-1101 than would be the case with lenalidomide. In the groups chosen for enrollment, it seems to me that use of an alkylating agent such as chlorambucil or of an as yet unproven mab such as GA-101 or unproven bcl-2 inhibitor such as ABT-263 would not be ideal choices either.
The course of events that you have predicted does seem likely, but will yield some useful information, especially as regards utility of GS-1101 at the 2 doses to be used in the expanded (“crossover”, if you will) study.
The real contests that we will need to see later will be PI3K inhibitors vs. BTK inhibitors &/or the use of combinations of such therapy, perhaps alternating use of each drug every 3 months or so to minimize toxicity and or to maximize efficacy.
ia5275:
Allopurinol and rasburicase protect the kidneys – as stated in my article as well.
Your other comments are thoughtful and well taken.
Hi Chaya– I’ve been on the R+CAL101 trial at MD Anderson since July of last year (2011). I’m currently on my last trial cycle, so at the trial’s end in June I’ll start “maintenance” CAL101 for an indefinite period. My protocol is identical to the Arm A of the upcoming East Coast trial: Initial 8 weekly Rituxan infusions, and CAL101 orally 300 mg/day. I didn’t need any other pharmaceuticals for TLS, uric acid or anything else.
I’m unmutated, 13q14. If I didn’t have objective evidence of CLL, I wouldn’t know that I have it. No nodes, spleen, liver, or any other symptoms. My CBC values are now pretty much in normal ranges. I do have low Immunoglobulins, but I haven’t caught any bugs. My bone marrow is 50% cleared of CLL cells.
I can think of no medical reason to compare single agent R to CAL in previously treated individuals. I’m sure the CAL group will continue to show very livable partial remissions, whereas the R group will eventually relapse, and be transferred over to the CAL Rx in this Phase III trial. My hunch is that they’re simply trying to hammer home the effectiveness of CAL for FDA approval purposes.
However, I’m beginning to see, and the very early data seems to infer, that CAL probably will not provide complete remissions. If a person stops CAL, their symptoms and levels will start to relapse. So I’ve started to believe that the inhibitors (I’m sure they’ll all have roughly similar results) as medicine to treat as in a chronic disease or deficiency– similar to diabetics who must take insulin, or those who must take some Rx to keep some malady at bay. Still, one can’t beat the results!
I’m assuming that within 10 years, chemotherapies will be passe, and we’ll all have the benefit of engineered T-cell CARS therapies. ~Art
Gulfportdoc:
You may be right about chemotherapy becoming passe in 10 years. I surely hope so.
As for kinase inhibitors becoming like insulin maintenance therapy for type 1 diabetics and late stage type 2 diabetics, I am less convinced. The long term adverse effect profiles for CAL-101 and PCI-32765 are as yet unknown.
What we have seen so far is not all benign. True, the early trials are all with late stage patients. But there is a disturbing trend in high grade pneumonia (inflammatory pneumonitis) and I have heard from a couple of patients with what can only be termed as inflammatory colitis of the gut. Diarrhea truly from hell. How will less far gone patients fare on these drugs? Only time and well designed clinical trials will tell.
Getting back to an earlier comment by ia5275: I was not suggesting a trial design that involves combining CAL-101 with Revlimid etc. I was merely suggesting that single agent Rituxan is perhaps not the best option available to folks who got randomized into the control arm of this trial. There is an ethical requirement that trials should not be designed such that control arm patients are short-changed in the process. In a better world control arm folks get the best standard of care presently available, and the experimental arm gets to be compared against that. As things stand, companies have learned the easy way of doing things is to compare against straw-man control arms.
But as I pointed out in my review, their follow-on trial gets people out of this dilemma.
Chaya: this might be naive, but would it make any sense to use these kanese inhibitors with leukapheresis? It just seems that it might be more effective than rituxin at getting rid of the flushed out cll cells and would by pass the kidneys.
Ambrose
p.s. pardon my spelling
Chaya,
You truly do so much for us. Calling the trial sponsers to clarify that pts. not doing well on the Rituxin arm have recourse to start the extension trial provided us with very important info. There are not enough ways to say thank you for all you do for us, but I am grateful.
Chris R
Thanks Chaya again for your diligence.
Regarding kinase side effects, a side note. Unless already been mentioned, I learned last week while applying for the NIH PCI trial, that any patient taking cumadin (warfarin) will not be accepted into the trial. It seems that blood thinners can cause bleeding in a very nasty place, the brain. I could not find online any exclusion criteria in the CAL trials, but surely I missed it.
Another side note: We both just now read “A Happy Ending” and it was inspiring, and we thank you both for the journal. There too we saw your new pup. It and he blew us away. As mentioned earlier, we too lost our black tri last Oct. Agonzingly we decided at our age not to try to “replace” him, Alas, STILL in our 70s, only 4 months later, we had a red tri puppy, every day thanking us for being us. We totally get your joy.
Sorry to get off topic.
As with any new treatment, side effects may rear their head at any time and the best thing I can do for my fellow patient is to let them know what has been experienced. My husband too experienced the dreaded inflamation of the lungs on the CAL 101 trial. This may not be a common event, but it is certainly life threatening if not recognized. A point to remember: your local GP, emergency room may not recognize what is happening. In our case I had to fight the emergency room doctor who could hear nothing wrong, until I demanded an xray. So in our case the first sign was a bad cough, and it slowly developed into a severe case. Once severe, our local hospital had no idea how to handle it.
In our case, my husband responds very well and quickly to Rituxan and allopurinol is a necessity. After his first Rituxan infusion and CAL 101 pill on the trial he had a severe case of tumor lysis and ended up in the emergency room when he became quite incoherent and ill. Some of these things will be ironed out as the trial goes on, and certainly not everyone will have these same reactions, but knowledge is power, so please just be aware.
Chaya,
It is with gratitude that I always read your articles, knowing how much knowledge and research you put into them to help those of us who don’t have the background to understand all the technical papers.
My husband has had SLL/CLL since 2001 and his remissions are now very short. We were considered for a trial, but then our doctor decided it was too risky. He is suggesting Campath. It’s been a while since you wrote about that drug. Any new news about it’s effectiveness for someone who has a lot of lymph node invovlement?
Chaya,
do you have any information about how Congress speeding up drug development(which it apparently agrees on) will affect the kinase inhibitor drug development quest or any other new CLL drug development?
howard5777:
I do not have any specific information about speeding up of new drug approvals. Like the rest of you, I will keep my fingers crossed and hope some of the red tape fades away. At the same time, I do not want FDA caving in to pharma industry pressures and approving dangerous or ineffective drugs. This watch dog agency is our primary line of defense against medical frauds, overly aggressive marketing, biased reporting of clinical trial results that are driven by greed and conflict of interest. We need new drug development, we need the creativity and drive of pharmaceutical industry and the researchers that test the drugs. But we also need protection from excesses.
Like everything in life, it is a fine balancing act.
I recently reread this excellent article and gained more insight. I agree that the patient in the experimental arm needs to take some prophylactic drugs like Bactrim, Acyclovir, Neulasta and Allopurinol but again how will the patient know to request(demand?) these medications if they do not know whether they are in fact on the experimental arm? What doctor would go along with this approach? I guess I could subject myself to these drugs in any event just in case but that is contrary to all good medical advice for the “placebo” arm. Seems like a real conundrum to me. Taking allopurinol initially seems like a low risk approach and presumably after the first cycle there would be ways for the clever patient to determine which arm they were in and take action accordingly. Again, nothing is simple.
Chaya,
Thank you for your continuing informative reviews of treatments. Two years ago I successfully had treatment with FCR. At that time whenever I read turned to clltopics, I thought that you were writing it directly to me.
Recently I decided to start my own research into the kinase inhibitors. I wanted to find and read the scientific articles, however I was stunned to find two online companies (selleckbio and activebio) offering to sell the drug online.
Any comment?
Marlene
Marlene:
I would be very, very cautious before buying drugs such as this from online companies. You would have no way of knowing whether they are selling you total garbage or efficacious drug. There are plenty of risks as it is in using drugs such kinase inhibitors presently in clinical trials. Taking these drugs outside of well conducted clinical trials, sourcing them from unknown online companies is really asking for trouble. My two cents.
Chaya, When ever I feel discouraged , you always make me feel hopeful. Thank you for being there…..
Sue H- ZAP70 pos,unmutated,trisomy 12,dx.2007, 3 txs of rituxin,FCR no remission
Chaya , Thank you for all of your wonderful words of wisdom. I will continue to read your remarks as I travel through this mysterious road of mystery.
Please don’t ever give up.
jeanette
I am participating in a single agent GA101 trial for previously untreated cll. I received 10 infusions between 5/8/12 and 10/2/12 and was determined to have a partial remission in early December based on blood counts and ct scan. I was diagnosed in 2003 at age 59 and received no treatment until the clinical trial. Treatment was recommended (FR) because a CLL-related mass which posed a risk of intestinal blockage was discovered by ct scan, colonoscopy and biopsy. I had not noticed those kind of symptoms. I note that the trial workup FISH test showed trisomy 12 and 17p53 deletion in 10% of bad cells where an earlier FISH test detected only trisomy 12. Bone marrow biopsy showed 80% bad cells. Side effects have been mild – flushing 15 minutes into the first infusion, low fever, some slight nausea and low fever for a couple days. After one week my white count dropped from 56 to 2.5, also my platelets dropped to 50 but quickly rebounded. Palpable lymph nodes diminished to maybe nothing. My blood counts are now normal and the ct scan I had in late November did not detect the threatening CLL-related intestinal mass. Alas the scan detected a 1.7×1.0 cm node in the mesentery which meant partial rather than complete remission so no bmb. I go in every three months until progression which I hope never occurs. But if it does I will let you know.
Well, I’m in the Phase III GS-1101 (was called CAL-101) trial with ofatumumab. I was randomised to receive Ofatumumab plus GS-1101. I’m doing great! No infusion related reactions, as Chaya said0 WBC rose as the white cells were flushed from the marrow, and is now falling. CLL-related fatigue now gone! Running, biking and weight lifting all improved. Just starting week 7.
Sincerely,
Malcolm
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