Arnie’s Rebounding World: The Clinical Trial
During the course of my treatments for multiple myeloma over the last few years, I have run the gambit of FDA-approved drugs.
After my initial induction therapy and stem cell transplant and a period of watchful waiting, I started on Revlimid (lenalidomide) and then added dexamethasone (Decadron).
After slowly relapsing on Revlimid/dexamethasone, I was switched to Velcade (bortezomib). After five months of Velcade, the response was very good, but I had to stop due to the side effects. So I went back to Revlimid/dexamethasone for maintenance.
When I again began to relapse, we added the Velcade back hoping the synergy of Velcade/Revlimid and dexamethasone would do the trick. Unfortunately the benefits of this regimen were short for me. After about five months of the 3-drug regimen, my numbers started to climb again.
In the span of four years, I had now pretty much exhausted the options of currently-approved novel therapies. It was decision time. My physicians recommended a clinical trial.
The sad reality of the current state of multiple myeloma treatment is that development of drug resistance and relapse is almost inevitable, and there are only a few approved drugs out there. There are, however, many, many more investigational drugs in the pipeline that are only available through clinical trials.
I am all in favor of helping advance the frontiers of multiple myeloma treatment, especially if it helps my disease. Additionally, there are some definite benefits to being in a clinical trial, but there are some big downsides as well.
Studies have shown somewhere between 25 percent to 50 percent of Phase 3 cancer trials will lead to successful new treatments. So not all drugs being tested in clinical trials are winners. Sometimes you’re just helping figure out what doesn’t work. Useful to the drug company, but doesn’t do much for you.
In my particular case, my doctors recommended pomalidomide (CC-4047), which is the third generation in the evolution of the drugs thalidomide (Thalomid) and Revlimid.
At Moffitt Cancer Center, where I am treated, they were actively enrolling patients in the Phase 2/3 pomalidomide trial. Everyone seemed to agree that this was a great drug and this was possibly the only opportunity I would have to get access to it until it was FDA approved.
After qualifying for a study, one of the first big drawbacks of the clinical trial is the “wash out” period. In order to get clean results on the effect of the drug, studies often require that you be off treatment for a period of time to wash out any other drug effects.
What this meant for me was as my disease was progressing, I had to sit and wait for a month and do nothing before I could be screened for the study and than wait another two weeks to be approved before I could start. This was maddening.
My reaction was, “You have to be kidding me. Six weeks of sitting and letting my disease get worse before I can even start the treatment.” The protocol was completely unyielding on this, despite begging and cajoling.
The next big issue with being in a clinical trial is “randomization.” Most clinical trials have at least two arms or options. Trials can compare the study drug to placebo or standard treatment, look at standard treatment with or without the addition of the study drug, evaluate different doses of the study drug, etc. Patients are randomly assigned to the different arms of the study. This is also unyielding. You don’t have any say in which arm you are assigned to, even if you believe one will be more effective than the other, and depending on the study design, you may not immediately even receive the new drug.
In the case of the pomalidomide study, the two options were pomalidomide alone or pomalidomide with dexamethasone. I already knew from my reading that the results were better with dexamethasone, and I was getting desperate. I was getting worse and wanted relief. No matter, I was randomly assigned to the pomalidomide alone arm.
So for the first month, I took pomalidomide alone. It was completely ineffective for me. My monoclonal protein level (M-spike) continued to climb. It felt like another month wasted. The pomalidomide study did allow for the addition of dexamethasone after the first month if pomalidomide alone was not effective.
The second month on pomalidomide and dexamethasone I began to see results, but not without side effects. I was dizzy, exhausted, and barely able to walk up stairs. My hemoglobin was dropping, but I was again out of luck. The study did not allow for transfusions or red blood cell stimulators until a certain level. It also did not yet allow for dose adjustments.
After another month of this, I was in dire straights. I went to the hospital and was admitted for pneumonia. “Oh yeah, we’re seeing a lot of that with this drug,” said the study nurse. Gee, thanks. The drug was stopped, and there was a huge rebound effect with even more aggressive return of my disease.
That ended my experience with my first clinical trial.
I know that having relapsing multiple myeloma means that I will likely need the new drugs in the pipeline and will need to be in other clinical trials in the future. Of course I’ll participate, but it isn’t always easy.
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Can't you have a bone marrow transplant? Arnie, I am going for one in September this year. A little nervous, but this isy second relapse and they recommend it.
Arnie: So sorry to hear this. My husband has been off treatment since 5/24, in Near CR. Recently (not long enough in Near CR, for me)his M-Spike began to creep back up.
He went on Monday for additional labs, to determine if treatment needs to start again or, if by some miracle, the M-Spike has gone back down.
And, I wonder.....if treatment must begin......will it work, again, like it did before? Will we be able to use Velcade/Dex, or will something else be necessary? And, if there's something else.....will it work?
Like the disease, it's a mystery.
Blessings and much luck!
Arnie-
If you ever read my column, you might have noticed I am a Moffitt patient also.
Sorry about all of the side-effects with the pom study. What's next for you? Please keep us updated--and good luck! Pat
How long did it take to relapse after your SCT?
You might consider tandem SCT (second SCT)...this seems to have a longer prognosis.
Arnie -- Thanks a lot for this piece. You point out the flaws in the way we myeloma patients can (or cannot) access new treatment drugs that are in clinical trials, or in the pipeline. And your personal experience is, I think, a great example of why things need to change.
Arnie: Thanks for pointing out the challenges with randomized trials. They take all the "individualization" out of therapy. Have you ever wondered whether the pol/dex combo was ineffective or the dose they gave you was ineffective? It isn't any fun being a guinea pig. Join me in trying to change the way trials are conducted.
Thanks for sharing your experiences Dr. Goodman! Earlier this year Dr. Omel shared his thoughts on the frustrations with clinical trials on The Beacon here:
http://tiny.cc/t0mj6
How can the MM community effect change...any ideas?
Steve
So sorry to hear about your poor response to the clinical trial. They do have a clinical trial at UAMS Multiple Myeloma Institute for Research and Therapy where they are using souped up killer cells from your own body to attack the myeloma. You may have heard recently in the news how this was successful with terminal patients with leukemia. They are now doing human trials and you need to be in your situation, relapsed and not responding to current medications. Dr. Van Ree was running the study and is returning in Oct. Currently Dr. Bijay Nair is running the study. It is a thought. This may be the wave of the future. In any event, hope for the best for you and will keep you in prayer.
Thanks for all your comments and thoughts. I haven't finished the story yet, but I did go on to have a second stem cell transplant after the pomalidimide trial. I will write more about that in a future post, but it did work pretty well. The clinical trial experience can be frustrating because as was noted there is no individualization. I do understand the pressures the drug companies are under, but there does need to some recognition of the patient as an individual. Don't get me wrong, clinical trials play a vital roll but go in with your eyes wide open.
Thanks for doing the trial, Dr Goodman... it's because of those like you that we have protocols that work, both now and going forward. It takes a level of courage to trust/hope that your participation in the trial will benefit not only the testers but you as well.
I think it is important to thell the WHOLE story, people read these comments who are new, and they feel anguish and pray for these people they do not know, and then were find out the whole story was not told.
If everybody could just be very honest.
Arnie: The chances to respond to Thalidomide after Revlimd fail are 20%. Good lack.