Pat’s Place: Clinical Trials Need To Include All Of Us
Just when you think you’ve got this myeloma thing figured out, there’s so much to learn all over again.
Looking ahead, most of us have an idea about what we’d do when we start running out of FDA-approved drugs to help us: join a clinical trial. And there are literally hundreds of them for multiple myeloma patients.
So no worries, right? Simply pick one from column A, B, or C, and away we go. Hopefully, our doctor can help us find one that is likely to work for us and recruiting patients close to home. After all, that’s what clinical trials are designed to do; help us live longer.
So why should I be surprised that sometimes it isn’t as easy as it sounds?
Have you had an allogeneic (donor) stem cell transplant? Sorry, most trials won’t let you in. Others exclude patients that have had two or more autologous stem cell transplants.
Are you a nonsecretor like me? Very few trials make allowances for us. Too tough to measure and standardize results, I guess.
Trouble is, the number of nonsecretors is increasing. It turns out that many late-stage myeloma patients become nonsecretors over time. Apparently, older myeloma cells tend to secrete less measurable protein.
Ironic, isn’t it? More and more patients are being excluded from trials at a time when there is a shortage of participants; researchers are begging for more. And, by excluding patients like these, many trials are inaccessible to those of us who need them most.
There are a few, outside-the-box, long-shot trials that allow one or more of the above categories to join. But, if you guessed they tend to be the ones least likely to help us most, you’re right.
I did learn about a new trial that may allow nonsecretors from a doctor at the Mayo Clinic in Jacksonville the other day. But it is only a Phase 1 trial, meaning the primary goal is to determine the safest and most effective dosing, not necessarily keep patients alive.
Get me in a Phase 2 or 3 trial, featuring one of the new immunotherapy drugs! But so far, I’m out of luck. I have been considering a modified allo trial, using engineered T-cells. But I’m concerned about the time commitment needed to do an allogeneic trial (three or four months away from home), as well as being limited from accessing more trials in the future. Also, it’s risky. The approach may minimize graft-versus-host disease (GVHD), which should make the transplant safer. But many myeloma experts believe there needs to be some graft-versus-tumor effect (which goes hand in hand with GVHD) in order for an allo to control multiple myeloma.
Which brings me to the million dollar question: Assuming a patient can get in to a trial, how will we know it’s the right trial for us?
Not having enough choices isn’t good. But too many options can be problematic, too. If you are fortunate to qualify for several different trials, how do you know which one may work best and help you most? Patients need better direction as to which trial to pick. Select the wrong trial near the end, and you may not get another shot.
May I make a few suggestions?
First, include all myeloma patients in clinical trials. It seems silly to exclude any late-stage patient from a trial. Researchers, drug companies, and patients need all the help they can get!
Second, our doctors need to be more knowledgeable about which trials may help us most. It shouldn’t be as difficult as it seems. If we’ve had a good (or not so good) experience with one or more drugs from a particular class, start there. I managed to locate several different clinical trials that seemed like good fits. For example, one used an FDA-approved drug that I hadn’t tried yet as part of the control arm, combined with an experimental immunotherapy drug I’d heard good things about in the experimental arm. Either way, I win! Unfortunately, that’s before I learned I didn’t qualify for this and so many other trials because of the nonsecretor thing.
Third, trial-related expenses should be covered for trial participants. I had been led to believe that my medical expenses would be covered after I enrolled in a clinical trial. Not always true! Remember the modified allo trial I referenced earlier? Researchers expect the patient to pay for the transplant – that’s the most expensive part. The trial will pay for modifying the donor T-cells to be injected back into the patient, but not the transplant itself.
We all understand that our healthcare system isn’t perfect. Unfortunately, neither is the way clinical trials are designed and enroll patients. Here’s hoping that more trials will begin accepting a wider variety of patients, providing better direction for when and why a patient should join, and paying for their trial-related expenses.
Clinical trials serve a dual purpose: to help bring new and more effective drugs to market, and to help save patients’ lives. Here’s hoping that researchers don’t get so caught up in selection criteria and the numbers that they forget about the life-saving part.
Feel good and keep smiling!
Pat Killingsworth is a multiple myeloma patient and columnist at The Myeloma Beacon. You can view a list of all his columns here.
If you are interested in writing a regular column for The Myeloma Beacon, please contact the Beacon team at .
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I think I understand why they do it...keeping the known factors (patients) as homogenous as possible. Also, a drug that kills too many patients gets bad PR and that kills the drug company. So they probably want the cream of the crop of eligible MM patients.
Seems there should be a way of signing along a dotted line where you understand the risks and accept the consequences. Also, this information would not become part of an official trial where it could hurt a drugs chances of being approved.
Sorry you're having to navigate these waters that most of us will have to also navigate someday.
Take care Pat. And just so you know, I am currently smiling and I feel pretty good--ha.
Pat, I'm with you. I'm also a late stage myeloma patient who is not eligible for most clinical trials (low counts due to 4 & 5 drug combo cocktails while trying to find trials/ have to show disease progression but if I do that I won't make it to the trial). If I read one more time about how more patients need to sign up for trials I'm going to scream. I'm healthy in all other ways except myeloma. This does not make sense to me.
Hi Pat,
This following item from your article caught my eye. "The approach may minimize graft-versus-host disease (GVHD), which should make the transplant safer. But many myeloma experts believe there needs to be some graft-versus-tumor effect (which goes hand in hand with GVHD) in order for an allo to control multiple myeloma."
I spoke with a young lady volunteering at the infusion center I go to. I asked her why she was volunteering and she said that she was a cancer survivor, leukemia. She had an allogeneic stem cell transplant; exact match from her sister. She also mentioned she did not have any GVHD and that worried her doctors for the reason you mentioned, but still she's now free of the cancer. So maybe the concerns doctors have about no GVHD, no cure isn't the last word.
All the best, Steve
Yes, Stan, I understand why researchers do it this way; you're right. But read Nancy's comment. Spot on. I'm in a similar situation. Never said making it better would be easy...
Steve's right, too. GVHD may not be necessary. Or maybe it is for some and not others?
Excellent article that echoes a comment my oncologist made a few appointments backs. He said it used to be that the life expectancy for myeloma patients was low for most--so he is not convinced the oncology world has a real understanding of what myeloma looks like 7 years, 10 years, 15 years out. "We rarely had to deal with that scenario." And as you point out, now that they have to deal with this issue, the clinical trials world is not prepared. I understand homogenous groups and the need for that in trials, but you'd think one could find enough patients in the late stages that appropriate trials could be conducted.
Pat, the timeliness of this article for me is perfect. Thank you!
April, glad you brought that up. I'm sure this is one of the points he was trying to make: the drugs we're using were never designed to be used for five years at a time! FDA safety testing for a lot shorter time. Still, what choice do we have? Even more choices! Bring on elotuzumab, ixazomib, daratumumab...
I am caregiver to my wife (IgG, 17p deletion, diagnosed 6 years ago).
None of the previous six courses of treatment was effective for more than six months, including a SCT, RVD, and Pom. She has been on a Phase 2/3 trial of Darma now for 14 months. The most effective treatment to date and seems to be approaching VGPR. Fingers crossed.
I recently completed a five week Coursera online course - Designing and Interpreting Clinical Trials - from Johns Hopkins. It's online and free.
I highly recommend it for better understanding the complexities that Researchers face when designing trials. Once armed with this knowledge, you may be able to identify more suitable trials for you and you will absolutely understand the parameters that restrain researchers.
My husband has high risk late stage myeloma. He was told repeatedly that he did not qualify for clinical trials because of his 20% kidney function. He was put on panobinostat a month ago. His light chain number was in the 300 range at the time and shot up to 26,435 in two weeks. Needless to say, we wished he never took the drug and that his doctor had tried Pomalyst, Kyprolis and dex instead, as he had told us that he would before panobinostat became available. Now he's out of options and told to look for hospice care.
Good advice, Harry! Here's hoping your wife stays in VGPR for a long, long time.
A pair of tough cases. So sorry Harry and Suzanne! Suzanne, did he eventually try Pomalyst and Kyprolis? Didn't help?
Pat,
I was recommended for a clinical trial to test the safety of dose escalation for Kyprolis to 56 mg/m2, double the current FDA recommendation. There are two arms, one high dose and the other low dose, with crossover to the higher dose with disease progression. I screened for everything, except they required a bone marrow biopsy with > 10% plasma cell involvement, and my biopsy came out 10%.
The requirement seemed kind of arbitrary and not that meaningful. It is my understanding that the distribution of cancer cells in the bone marrow is not homogeneous, so a sample in one area can be really low and a sample from another area not far away can be really high, so what is the point of a >10% threshold for a trial? So I was not admitted to the trial and it was suggested maybe a second bone marrow biopsy might come out >10%. I thought it was a long shot, but I said, "Why not?"
On the day I was to get my second biopsy, a revision to the trial came in eliminating the >10% requirement, so I did not need to do the second bone marrow biopsy. It seems that the trial organizers may have gotten some feedback from a number of participating organizations questioning the >10% requirement. But then, upon careful examination of all the labs I had taken to screen for the trial and when I had done them, and because I was not admitted to the trial a week earlier after my first bone marrow biopsy was done, it turns out all my labs would expire, they did not fall into the time period required before the earliest I could start treatment. I would need to rescreen from scratch and redo everything I had done before, including the PET scan, whole body X-ray, etc. And I had already made travel plans for the week off period based on the schedule of treatment I was expected to have if I had started the trial as expected.
At this time things are in limbo and I do not expect I will be in the trial now. It is getting too complicated. I guess the good news is that, other than high kappa light chains, my labs were pretty good. The PET Scan came out clean and the whole body X-ray showed no change. So while it appears my myeloma is relapsing, it appears not to be that aggressive. It may be that the higher dose Kyprolis would not be a good thing for me at this time anyway.
It is kind of frustrating. I think I would be the ideal candidate they are looking for in this trial to get desirable results. I am in pretty good health for having myeloma. I swam 12,000 yards last week and biked 42 miles on Saturday. My heart numbers are in really good shape. It seems in your case you seem to be too difficult and complex, while in my case not difficult enough. It would be helpful if they had put a little more thought into what is really necessary or not to screen for this trial upfront.
Pat,
I understand your position. My husband has not qualified for even one trial – we have tried for three now – usually because his platelet counts have been so low, but other factors as well, such as the amount of previous treatments, etc. Now with him being in late state MM and the way he relapsed after his second SCT after less than 6 weeks with a large extramedullary plasmacytoma in his left pelvic region (now 8 more since February spread all over his body); radiation twice, on three separate plasmacytomas; and now looking like another round of radiation on one of newest three (we find out this week), as well as Velcade and cyclo weekly and steroids every other day (he is still getting new extramedullary plasmacytomas) – we are running out of viable options.
It is hard enough to deal with the prognosis, but we often talk between us – "Why don't they offer these trial drugs to patients that have little to no options as a side trial, especially when they are dying anyways? It could prolong their lives". How can it hurt their trials if these patients are excluded from the main trial data and it might give the pharmaceutical companies additional information to help these patients?
It is so frustrating, especially here in Canada where we still can't get carfilzomib, which is only available on clinical trial, and again my husband does not qualify. We need more pharmaceutical companies that provide these trial drugs on a compassionate basis and our governments to allow it (my husband can't get carfilzomib on a compassionate basis as Health Canada has blocked it, but in this case, the pharmaceutical company has it available for compassionate reasons). Way too much red tape!
My frustration rant for the day - my apologies.
We are hoping for the best for you and for you to keep fighting - you give a lot of people hope and very valuable information.
Sondra, please excuse me commenting on Pat's column, but I had a thought about this. You don't mention if your husband has tried Pomalyst yet. It is now approved and funded for myeloma in Ontario, New Brunswick and Alberta. it may be funded in other provinces or territories too, that I have not yet seen announcements for. It was/is available by a 'special access' program before that too. You could ask your myeloma specialist about this. Hope that helps you.
He was given carfilzomib with dex, which did not work at all. Pomalyst worked wonderfully after just 3 cycles and was so close to putting him in a complete response until he complained that it caused his neuropathy to move from his feet to his knees, which resulted in the doctor lowering the dose from 4 mg to 1 mg. I pleaded not to do it because I had read Dr. Shah's clinical trial results where he stated that 1 mg did not work and he was right, his light chain shot up to 3000 +. He was then hospitalized for 3 days of continual high doses of Cytoxan which dropped them down to 400 but resulted in his platelets becoming so low, he could not have the second round.
We were told that he would be put on carfilzomib, Pomalyst and dex, which we were assured would work well together, unlike given individually, but was changed to panobinostat when – unfortunately for my husband – it was approved the week he was slated to start the combination of carfilzomib and Pomalyst.
Hi Nancy, yes he was on Pomalyst from late February to early May 2014 (within 2 weeks of if being approved in Canada) but his disease progressed rapidly while on it for the 3 rounds, so they put him on CyBorD for 5 rounds and he achieved good partial remission and had the second SCT in October 2014.
Sorry to hear that Sondra, I can see why you are frustrated about chemotherapies then. I think that Kyprolis was approved in the US before the phase 3 trials were completed. There was a phase 3 trial called ASPIRE, from which Amgen has applied to the EU for approval, but apparently not to Health Canada. At least I haven't heard anything about that yet. I imagine you are working with a myeloma specialist, who could advise you to any other trials. Best wishes and I hope you can find a way around this problem.
Sorry you had to go through all of that, Eric. Not sure you intended to or not, but you made my point!
Nice to hear from a pair of Canadians. Sorry things aren't tilting your way, Sondra. If anyone can help, Nancy can. But yes, again, this time Sondra is making my point. From time to time I hear people in the myeloma community referencing a "clinical trial of one." One way to try that is through the FDA's Compassionate Use Program. That way a patient can get a key drug without clinical trial run-around. Supposedly its becoming easier to do this. Otherwise we're simply exchanging one "run-around" for another...
Before I sign off for the evening, I need to share how disturbing and disappointing many of these situations are to me. I understand clinical trials are primarily designed to help drug manufacturers and/or academics get the results they need to help move a therapy forward. But let's not leave patients in the wake! Why not make a drug available to them, whether they qualify for a trial or not? I understand there can be safety issues. But if we're dying, loosen things up!
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