AG221 Trial Comes To An End

T-shirts given to blood donors during the Battle of the Badges, Beavercreek, Ohio. Donors were entered into a drawing for a trip to Alaska-therefore the Moose theme on the T-shirt!

Since the last post, Todd had another blood transfusion and a platelet transfusion on Wednesday August 31, 2016. His platelets were at 28,000, not below the prescribed < 10,000 to get a platelet transfusion, but he got platelets to boost his counts prior to a much needed dentist appointment to fill a few cavities the following day, Thursday, September 1. His hemoglobin was back down to 7.5 just about 9 days after his last transfusion on August 22, 2016, when he was transfused with 2 units of blood.

Our local fire and police department was sponsoring an annual blood donation drive called the "Battle of the Badges" on August 29, 2016, where blood donors show up for the police department or fire department to see which group can donate the most blood. I decided to donate for the first time in my life!  I've wanted to donate or organize a drive ever since Todd was first diagnosed with MDS and also when he was transfusion dependent the Spring of 2015, but I never did. For this event, I scheduled a time to donate after I got off work. I learned so much about the process:

• you need to drink lots of water the day of donation; 
• it takes about an hour to register and go through the screening process;
• there is a list of medications, mostly blood thinners, that should not be taken so many hours prior to donating;
• I was worried that I would be disallowed to donate after checking "yes" to having traveled outside the U.S. in the past 3 years, but once I talked with the nurse during screening, she said they were really only concerned about travel outside in the past year in certain countries, especially extended stays. We had gone to the Dominican Republic in the spring of 2014, prior to Todd's chemo and transplant. (I had to look it up, it seemed like longer ago than that!). 
•  They also had to prick my finger and test my hemoglobin. Mine was at 12.5 the minimum needed to donate. (Low end of normal but I passed!)
• I did not eat before I went and I guess that is not desirable!  Especially for a first time donor. They wanted me to go eat the proffered chili, cookies, and orange juice before donating, but I was worried about getting  home to Todd and Ellie who also needed to eat. So, instead, she insisted I ate something before I left.  She actually gave me permission to "pig out" when I got home! See: First time donors
• since 2007, women who have had children are no longer allowed to donate just platelets unless they have been grandfathered in, meaning they have been already a regular platelet donor prior to this date.   See: http://givingblood.org/about-blood/blood-testing.aspx
• The actual donation only takes about 15 minutes.

Everything went great! The nurses said they had a great turnout and they made sure to tell each donor that their donation could save 3 lives! They can separate your pint of donated blood into platelets, red cells, and plasma.  I was so happy to see all the selfless people who were there to donate, knowing Todd was needing 1-2 units almost every week, that I was ready to cry tears of joy!  The nurses also thanked each person for their donation.  I personally wanted to thank each donor too!!!!  The whole experience was so touching to me knowing Todd is needing almost weekly transfusions, that now I want to organize a blood drive in his honor!  Todd would not receive the exact blood donated, but it would go to our community blood bank, where Soin Medical Center gets their supply.  Will those who are local begin to consider donating?  I pray you will!   Stay tuned.  In the meantime, check out this link: Red Cross Blood Donor Eligibility Criteria

"Although an estimated 38 percent of the U.S. population is eligible to donate blood at any given time, less than 10% of that eligible population actually do each year."

-The American National Red Cross. 2016

  
Cleveland Clinic Trial Appointment Cycle 19, Day 1

Today's appointment at the Cleveland Clinic for his regular trial appointment and treatment was rushed. Since Monday was Labor Day,  many of the patients that had appointments for that day were deferred to today. The day started out unsettling.  First, we were told that the person scheduled to do his bone marrow biopsy called in sick. So, they were afraid they were going to have to reschedule it for another day! I'm glad the sick staff member stayed home, but I was upset that Todd may not be able to get the biopsy today!  I told Sam, his trial nurse, that any other time it would not have been a big deal, but there was so much riding on the results of this biopsy , i.e.  pursuing another treatment options, that I really didn't want it put-off nor for us to have to return in the next few days. She understood and said she would see what she could do. We had to wait about an hour to get labs and another hour to get into a treatment room. Unlike his local office, they can type and screen him for transfusion during his lab appointment, so this saved us some time.  After running behind two hours from all the waiting, we had doctors, nurses, and the pulmonary technician, all trying to come into his treatment room during his transfusion. It was crazy. 

His CBC showed his hemoglobin at 8.3, platelets at 27,000, Whites at .86 and ANCs at .67 (hovering close to neutropenia .5).  There was some real concern about the low white count and ANCs knowing that these low counts make him more susceptible to infections. They decided to give him one unit of blood since he was below 8.5 and probably would not be able to make it until next Wednesday to get a transfusion, when he goes to the local oncologist.  They were also concerned that if he had not received platelets last week that he would have likely would have needed them today. 

Luckily, Sam was able to get his bone marrow biopsy scheduled for around 3:00 in the afternoon. He normally doesn't take the "pre-meds" before the procedure, since he has had so many biopsies and knows what to expect, but today he took them. 

Unfortunately though, the results of the genetic blood tests done last week had not come back for review. So, we will have to wait until next week for both the biopsy results and the genetic panel.

In the meantime, Dr. Hamilton was fully convinced that the trial drug AG221, he has been on for the last 18 months, was no longer providing any response. In addition, the increased nausea and fatigue were only suppressing his appetite and desire to eat. He is still losing weight and there is no reason to continue the drug if it's not helping and prevents him from getting the nutrition he needs.

Another consideration for stopping the drug now is that it would allow a "wash out" required period of time off the drug before beginning a new trial or another treatment.

"For all these reasons, Todd was taken off  of the trial drug AG221 as of today."

For all these reasons, Todd was taken off of the trial drug AG221 as of today.  His nurse Sam will start the paperwork to close out his trial. I will be sad to lose Sam as Todd's nurse, since she only works with trial patients. She has been so good to us! She will be able to help us temporarily, until Todd starts a new treatment, and she has assured me that we will be in experienced hands in the future.

Todd wasn't able to get his Echo cardiogram appointment in today though; and it has to be done at the trial facility, meaning Cleveland Clinic. So, Sam was able to get an extension to have it done when we come back to discuss his test results and the start of a new treatment. 

So, after 18 months of visits for the trial, what will we do now?  How often will he need to go to the Cleveland Clinic? What are the treatment options?  As for visits to Dr Hamilton at CC, they will be scheduled as needed. No more mandatory 2 week blood draws, no more monthly EKGs, no more Echocardiograms and biopsies every two months. We were asked if Todd would be willing to allow these tests to continue for follow-up research purposes for trial study, but we haven't made a decision yet to commit to these since we live so far away and would be bound to do them. We will also lose the reimbursements for our expenses and hereafter will have to pay for any drugs needed that are on the market (like Revlimid) unless they can be obtained through another trial. In my last post, I mentioned the high cost of the drug Revlimid. Sam requested a quote from the drug company Celgene outlining the portion our current insurance would cover and/or what kind of assistance we could receive from them, but she hasn't heard back from them yet. I'm not sure it will matter, as Todd will be forced to apply for Medicare next month by Obamacare. Who knows what will be covered on Medicare and if we will have to purchase some kind of Medicare supplemental insurance to pay for what it won't cover. 

Other treatment options include going back on the monthly chemo drug Vidaza or maybe even a combination of Vidaza and Revlimid. Vidaza targets blast cells and Revlimid works by increasing red blood counts by working against the 5q cytogenetic chromosomal deletion that causes the anemia, and therefore the need for transfusions. 

 I feel like I need to start researching more trial options. Dr. Hamilton is still planning on talking to Dr. Stein and getting his insight after the genetic panel and biopsy results come back.  If Todd has both the IDH-1 and IDH-2 genetic mutations, he would be eligible for the trial drug AG881, which would be another option, albeit, a complicated one as we would have to travel to one of the 5 trial locations in the U.S. none of which are within a driving distance of less than 6 hours.

Todd will need to return to his local oncologist one week from today, September 24, 2016 to check blood counts.  Hopefully, we will have test results back and be able to make a consult appointment with Dr. Hamilton at the Cleveland Clinic too.

We appreciate your prayers and support.  I know Todd would deeply appreciate your phone calls. He lays around a lot because he is so tired and we rarely go out.  He really needs the encouragement.  He said that becoming transfusion dependent again brings back bad memories of when he was so sick after his failed transplant.  It is a vicious cycle of feeling his energy drain away more and more every day, until he can no longer put off another transfusion.  A special dish or treat might tempt him to eat for those who prefer to cook or bake.  A card, email, or text would also help boost his morale.  If you prefer to visit, please contact us first.  We ask that all visitors make sure they are in good health and haven't been exposed to sickness especially since his immune system is so low.  And, because he sometimes sleeps or take naps throughout the day, it might be best to call first before coming over, so you don't catch him sleeping.  I think it would be especially nice to receive visitors while I am gone at work during the day; that is when he is often alone now that the kids are all back in school.  It is also the time of the day he goes without eating.

God Bless!

Transfusion Dependency Continues.

Todd was tired and ready for a transfusion on our way to Cleveland Clinic August 17, 2016. The had a full day scheduled for him so we needed to start the day early which meant going up the night before. We usually stay at the Hope Lodge in situations like this but now that I'm working full time it is difficult to get there by 7 pm, the latest check in time. I would have had to take off work early on Tuesday in addition to taking off that Wednesday all day. Instead, Todd made hotel arrangements through the Priceline website. If you have never used it, you bid on a room for a certain price. But you have no choice of what hotel you end up with and there are no refunds.

We ended up with the Hilton Garden Inn Downtown Cleveland near the ball stadium. Sounded good. Unfortunately, we got a late start and didn't arrive until almost 11:00 after the long drive. Todd was exhausted. We went to our room and realized it reeked of cigarette smoke. We went back to the desk and tried to explain that Todd was a cancer patient, already didn't feel good and had a cough and we couldn't stay in that room. They informed us that it was a smoking room and that they couldn't move us because the entire hotel was full (which I find hard to believe on a Tuesday night).  They only offered to spray the room with a scent or put in an ozone filter machine, but that it would take hours!  I told them that neither option would rid the room of the smell plus he was exhausted and needed to lay down now. They refused to give us a refund saying their hands were tied because we booked through Priceline. I appealed to their moral obligation to do the right thing but once again said there was no other room. We also challenged the hotel for having smoking rooms in the first place when Ohio has been smoke free for over 15 years!  They said that since they were renting out a private space they could get around the laws and that they plan on getting rid of the smoking rooms when they remodel in the future. 

I don't mean to offend smokers. I have loved many people who were smokers,  most of them having died from the side effects. However, this is the reason why the laws are in place in Ohio: to protect non-smokers who have no choice in the matter. Especially sick people and children. Most smokers I know are conscientious and would gladly smoke outside. But this business wanted to make money on those smoking rooms they were having trouble selling. 

We said that Priceline listed the room as a non-smoking room, but the hotel insisted that they tell Priceline it may be a smoking room and it is Priceline's responsibility to tell consumers. I tried calling another hotel we had stayed at before. The entire hotel was non-smoking and they had a room at the Cleveland Clinic rate available but Todd was too exhausted to go. So we had to endure a night of smoke smell and no curtains. I called the GM but got voicemail. He called me back the next day while we were at the Clinic to offer us a free room but I refused.  I didn't want a free room then. He said it that every single room in the hotel that night was booked. I congratulated him and told him they apparently didn't need our patronage if they are that busy on a Tuesday night. I told him I don't want to stay anywhere that is not smoke free and I said with one in three people getting cancer it was likely he or the men working that night may have a sick family member and may be in our shoes one day. We showered, dressed, and tried to get out of there as fast as possible. I didn't want to walk around smelling like smoke all day!

When we arrived at the Clinic, Todd had to start his day of appointments with a few tests on his lungs, including a pulmonary function test.  We saw the pulmonary physician.  He asked several questions and reviewed the results of his prior lung CT in addition to the morning’s tests and said nothing looked suspicious.  He had no idea what was causing Todd’s cough.  He prescribed him some cough medication, but that was it. 

Next, was lab work.  They were going to give him at least one unit of blood even if his hemoglobin wasn’t below 8.0.  It had been hovering around 8.1 -8.3; not enough to get a transfusion but still not enough to give him energy.   Originally, the trial nurse didn’t have a treatment appointment scheduled for a transfusion, but on the Monday before, I knew he wasn’t feeling good and would likely need it. So, she was able to add it to the schedule.  It was a good thing, because he did need it.  His hemoglobin had dropped to 7.5 and they were going to give him 2 units.  We were waiting for the type and screen and results to come back when Sam the trial nurse and Dr. Hamilton came in to see him.  We were disappointed that all his counts had once again dropped even more:

Whites had dropped to 1.46; ANCs to .95, and platelets to 31,000. 

She thought it was likely that the trial drug AG-221 was losing its effectiveness.  There was just no other explanation. I was confounded when Dr. Hamilton started talking about other options: Revlimid (for patients with Chromosomal Deletion 5q), and even harsh chemo and a second transplant!  I didn’t understand why we were discussing this now; neither one of these last two options would have a high success rate at this point.  I thought we should have at least Revlimid to try and/or going back on Vidaza again before bringing those options up. She was also concerned that he was starting to lose a little weight.

While getting his transfusion, the respiratory therapist came in and gave him his Pentamidine Breathing Treatment and another trial nurse came in for his EKG.  He had to miss two other appointments, because of course, everyone was running behind and we couldn’t get to either.  One was to receive more immunizations.  I wasn’t upset about missing this one.  I didn’t think it was a good idea anyway; to be getting more immunizations with his counts so low. 

We drove through thunderstorms and finally got home around 9 p.m.  I was hoping he would start feeling better right away, but the next day, he felt faint and couldn’t drive home from a haircut.  Luckily he was near his mother’s house and stopped there to take a rest and then drove home a couple of hours later.  That day and the next day he still felt puny and didn’t get out of bed much. 

This concerned me, so on Thursday, I put a call into the doctor and she called me back on Friday morning, August 12.  I told her about Todd’s lack of energy and nausea.  I also asked why she brought up chemo and a second transplant.  She said she just wanted to discuss all of his options.  She said that if Todd started needing transfusions more often, that she would consider taking him off the trial drug and starting the Revlimid, but not until then. 

By Friday afternoon, I was concerned and decided to call Dr. Eytan Stein at Memorial Sloan Kettering in New York City. He saw Todd before he started on the AG221 and I knew he had a lot of trial experience with the drug.  I wanted to pick his brain about other options.  I left a message and by that evening, he called me on my cell phone at home.  We discussed Todd’s case and current condition, the great response he had with AG221, and then the steady decline of his blood counts.  He was surprised at Todd’s great results with the drug, but then said that they had noticed that some patients who stopped responding to AG221 who had the IDH-2 genetic mutation, often developed an IDH-1 mutation in addition.  For these patients, there was a new trial drug AG881.  He asked me to have Todd’s bone marrow biopsy, doctor’s notes, and latest genetic panel sent to his office for him to review.  

I sent an email to Sam, his Trial Nurse at Cleveland Clinic to request they send the information to Dr. Stein.  Unfortunately, they hadn’t done a genetic mutation panel since May 2015, so they would have to wait until his next scheduled bone marrow biopsy to get this, but she sent what they had.  We were charged $45 for this request, but I will pay it happily.  I decided last year that I would do whatever it takes, including seeing the best doctors, traveling to any hospital to help him. 

I talked to Sam on August 17, the following Wednesday and told that I didn’t want to step on Dr. Hamilton’s toes, but that I really wanted to hear what Dr. Stein had seen in his trials and practice that could be of any help to Todd.  I also asked her to call in blood work orders, as Todd was still feeling poorly and I feared he needed another transfusion.  She called them in for the next day, Thiursday, so if he needed a transfusion, he could get it on Friday before the weekend.  Stubborn Todd however, refused to go then.  He wanted to wait until Monday, August 22, 2016 to go have his blood work done that way they could use it for his trial draw and wouldn’t have to repeat blood work scheduled on Wednesday August 24, for his trial draw for Cycle 18, Day 15.  Well, that was a mistake, one he admitted later.  He felt horrible all weekend. He didn’t drive, leave the house, or get out of bed.  The Olympics were on TV, so that kept him entertained in bed between naps.  By early Sunday night, his cheeks looked red so I grabbed the thermometer!  He was running a low-grade fever or 100.3; enough to go the emergency room.  He refused to go. I conceded as we both thought it was just a neutropenic fever.  We kept an eye on it and it was down to 99.6 before bed.

In the morning, he took a shower and his temperature was normal.  I took him to Soin Medical Center for a nurse’s visit in the Cancer Center there on the 4^th floor at the appointed time of 8:30 a.m.  His nurse also felt that he had waited too long to come in and thought he looked especially jaundiced since he was so pale (low hemoglobin).  She said that she wasn’t going to let that happen again and scheduled him for another blood draw to check counts for next week, August 31, 2016. I was glad for that.  After waiting almost 2 hours since we arrived, we finally got his counts back:

Hemoglobin was a low 7.0.  Whites 1.0.  Platelets 22,000 (transfusion of platelets needed at 15,000) and ANCs at .7 (neutropenic at .5).  

She gave him all the necessary warnings about his care: Careful with hot showers because of getting petechia spots, bleeding while shaving, etc.  When she went to schedule the transfusion, she came back and said she set it up for the next day, thinking that was what he would want.  I was upset at this!  I told her that he needed the transfusion TODAY! And that we were not leaving without one; he couldn’t wait.  Todd was so sick, he didn’t feel like arguing with her; so I did!  She told us that it would take 3 hours for the type and screen, longer to get the blood ready, do the transfusions, and that we wouldn’t be done til 8:00 p.m. that evening.  I told her I didn’t care and questioned why she didn’t do the type and screen when she drew blood.  He had already told her that he knew he was going to need a transfusion.  We had already been there for 2 hours!  She said she can’t type and screen for blood type until the initial blood results come back and she gets orders for the transfusion.  To me, this could have been done at the same time; this is what they do at the Cleveland Clinic and I told her so.  Long story short, I was so glad that I took him and told my boss I would be late.  If not, I know he would have went home and waited the next day.  Then, he would have had another day of feeling  bad and getting up early again. 

It didn’t end up being as bad as she thought.  I wheeled him done to the Universal Care Area and they checked him in right away and got him a bed.  I made sure he ordered lunch, then I went into work for a few hours.  They had the first unit to him by 1:24 p.m.  I went back to the hospital about 4:20 and he was finishing his second unit.  We were out of there by 5:00 p.m.!

This is why the caregiver needs to be present to help with the decisions that the sick patient don’t feel like dealing with.  He didn’t want to argue with the nurse; he didn’t feel like it!  But I did!  He told me later that he was glad that he didn’t wait until the next day.  And unknown to the nurse, we were out 3 hours earlier than her prediction! 

That afternoon, I talked to Sam, his trial nurse at the Cleveland Clinic and let her know his numbers and that he received 2 units of blood.  She said that she was feeling pretty sure that he was losing his response to the AG221 and would talk to Dr. Hamilton.  She was also concerned with his low white and ANC counts and would also discuss putting him back on his Cipro antibiotic as a preventative measure.  After talking to Dr. Hamilton, Todd was ordered to take his Cipro 2x a day and we were told that Dr. Hamilton was going to talk to Dr. Stein at Memorial Sloan Kettering to discuss Todd’s case and the option of taking him off of the trial drug AG221 and putting him on Revlimid. 

The transfusion seemed to help.  He was able to get around yesterday and even drive.  I am feeling a sense of urgency to get his medication changed and was greatly relieved that the two doctors are going to talk.  

The trial for AG881 is only available at 5 US locations: New York, Chicago, Boston, Aurora Colorado, and Texas. We won’t be able to find out if he eligible until he has the genetic panel processed on his next bone marrow biopsy at the Cleveland Clinic at his next appointment on September 7, 2016.  Then, it may take a few weeks to get the results back.  I’m hoping in the meantime that they can start him on Revlimid.

Did I mention that Revlimid (Lenalidomide) is on the market already and that it is very expensive?  According to Wikipedia, the cost for one year’s use was about $163,381.00 in 2012. (Wikipedia, 2016). Drugs.com quotes a 10 mg tablet, the starting dose for MDS patients at $16,457.14 for one month’s dose of 28 tablets!  (Drugs.com. 2016). I’m praying we will not have to pay all of that between insurance and a request to the drug company, Celgene, to buy it at a reduced price.  Of course, there is no generic available.

I'll post after blood work next week. Until I continue with my mantra:  Whatever it takes!

For More Information: 

Alsumidaie, M. January 2, 2015.  “The Cost of Saving a Cancer Patient’s Life” Applied Clinical Trials. Web. Retrieved from: http://www.appliedclinicaltrialsonline.com/cost-saving-cancer-patients-life-analysis-celgenes-revlimid

Celgene.com. May 2015. “Celgene Patient Support for Revlimid” Web.  Retrieved from: http://www.celgenepatientsupport.com/revlimid-patient/

ClinicalTrials.gov. August 23, 2016.  “Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation.” Web.  Retrieved from: https://clinicaltrials.gov/ct2/show/NCT02492737

Drugs.com “Revlimid Prices, Coupons and Patient Assistance Programs.” August 8, 2016.   Web. Retrieved from:  https://www.drugs.com/price-guide/revlimid

Wikipedia. Lenalidomide (Revlimid).  August 24, 2016. Footnote 2, 2012.  Web.  Retrieved from: https://en.wikipedia.org/wiki/Lenalidomide

Appointment at Memorial Sloan Kettering

There is so much to say I don't know where to start and what to include in this post. 

First, I need to give a shout-out to The Corporate Angel Network. I can't say enough good things about our experience so far. I spent time on the phone last week coordinating the appointment, securing a hotel, and waiting to hear about flights. 

We got the call Thursday that they got us a flight into Terboro Airport, NJ leaving out of Columbus, OH. They arranged for a car to pick us up at the airport and drive us to our hotel into New York City. We had to pay for the trip/car but it was so nice to let an experienced driver navigate the narrow lanes, traffic jams, constant honking, and aggressive drivers. 

On Friday,March 20, 2015 we got a call that the Angel network had secured us a flight back on Tuesday morning, March 24, and a free shuttle ride back to the airport. We would only have to pay a cab to get us to the shuttle location before 7 am. The flight would return back to Columbus so we would be able to drive ourselves to the airport and leave our car. 

Meanwhile, in Dayton they wanted to  give him IV antibiotics for seven days so they had to schedule around our trip 

We arrived an hour early to the independent Flight company an hour early. It was so nice not to have to go through security, put our liquids in small bottles, and be exposed to all the people at a public airport. The pilots were so nice and made us feel welcome. The  company members, whose flight we were on with, were so gracious and hospitable to us. The flight from Columbus only took 1 hour!  We landed and our car arrived shortly and took us to our hotel, The Bently, in the upper east side of Manhattan, which is only four short blocks from the hospital. We didn't have time to go to get food at a restaurant, so we grabbed a bite at the hospital's cafeteria. The appointment was at 2:00 pm. 

The space inside the hospital was very tight, which makes sense for a prime real estate area in New York. The staff were all extremely friendly and accommodating. I also liked their policy of asking everyone to wear masks, including family members in the Cancer office waiting rooms. They also provide rubber gloves for patients who don't want to touch anything. 

We didn't have to wait long to see Dr. Stein. He wasn't anything like I thought he would be. He was short, friendly, personable, honest, and straight-forward. He asked Todd to recount his medical history from the time of diagnosis in October 2011 to present. Then he gave us the opportunity to ask questions, which I had a list of!  

I started with asking him about his opinion to do a second transplant or not. He said it doesn't matter whether to do the second transplant now or in the future. He felt that Todd would still have the same results. He asked us if we were aware of second transplant outcomes. I said yes, they weren't good. He said that's right. According to the published reports, second transplants have a success rate of 5% to 10% and he felt those numbers were generous. 

I asked if Todd would be a good candidate then for the study and he said so far everything looked good. I also asked if there would be a better study out there besides this one, and he said no.  For Todd's MDS with the IDH2 gene mutation, this was the right one. 

We asked if we could start the study here and then transfer to another closer study location and he said yes. According to his sources, Cleveland might be up and running by mid-April at best. 

I asked if the drug was working for him, could he stay on it indefinitely and he said yes. They would continue to administer it to him throughout the additional phases of the study as long as there were no complications or adverse events (AE). Todd could continue transfusions and his current medications without any restrictions. 

When I asked about how often we would need to return for testing throughout the study, his answer surprised me; it was a bit more often than I had anticipated. The first month, we would be required to be present once a week. After that, every 15 days or twice per month. Testing on days 1 and 16 the first month would be the most intense with testing lasting 10 hours each day. He advised us to be prepared to stay an extra day afterwards to have some recovery time before flying home. 

When I asked the most important question: What could we expect from the drug that would help Todd and how soon he could start it, he began by saying that they are not sure how sustainable the response would  be. They hadn't got that far along yet in the studies.  So far, they have had patients still having positive results for as long as 14 months. He was clear to say that the drug should not be considered "curative."  He said the goals he would like to achieve in Todd's case would be to get his counts high enough to get him off of transfusions and to get his white count up past the point of being neutropenic. Blast counts at this point wasn't considered a major issue, since they were already low at 3%. The good news is that the drug can create healthy neutrophils from the blast cells, because it allows them to mature. 

He was very frank with us when I asked him what his opinion was regarding Todd's prognosis. Todd's BMT doctor just danced around the issue, and we wanted to know the truth. He regretted to tell us that relapsing within the 100 day period post-bone marrow transplant was detrimental and that Todd's only real hope for a curative treatment was the transplant. I cried and said why didn't the transplant work!  Everything was ideal going into it. I said I wish we hadn't done the transplant and it only seemed to make things worse. He assured us that we did the right thing in pursuing the transplant. There was no doubt in his mind that he would have recommended the transplant too, even if it was for a family member; he would have done the same thing.   It's so frustrating and hard not to ask WHY???

I asked him what was the difference  between staying on monthly rounds of Vidaza or doing the trial drug. He said that after looking at Todd's blood work, it didn't look like the Vidaza was really working. His platelets have come up but his other counts are still down. He also asked us if we know how sustainable Vidaza is, and we acknowledged that there would likely be a point where he would no longer respond to Vidaza. He agreed. In all fairness though, I had learned that it takes 4-6 cycles of Vidaza to reap the best benefits and Todd only had 3. 

With Todd's MDS, his blast counts have never been out of control or escalated to AML (>20%), but that's not what is affecting Todd's condition. Right now it's the low blood counts, especially his low white and neutrophil counts. This puts him at such a high risk of infection. As a matter of fact, he put it bluntly that for most patients in Todd's condition, infection is the most likely cause of death. The doctors are doing what they can to prevent this scenario by giving him antibiotics and antiviral medication. Monitoring his temperature is crucial. It is often the first sign of infection. If caught early, they can treat it more effectively. 

As to the costs, we are responsible for the preliminary screening, which our insurance should cover. Once he has been deemed eligible for the study, the drug company will pay for tests and treatments associated with the trial. In addition, they will help out with travel expenses up to a certain amount. 

So far there are at least 73 patients currently on the drug officially. It is a pill taken usually once or twice a day. We will be notified what amount and dosage Todd will take. When I asked about side effects he said that there have been some. Mainly an increase in bilirubin, but no major complaints of nausea or diarrhea. Among the AEs there have been some concerns with heart and lung problems. 

This is why they run all of the baseline tests: to establish how his organs are prior to the study and if there are any significant changes that could be caused from the drug. 

We asked how soon Todd could enroll and he said it takes about a week to sign, screen, and receive eligibility status. We asked if we could start by signing the consents that day, but he said no. Apparently, you can't see the doctor and sign the consents the same day. (Might look like Coercion). He asked if we could stay another day or two so we could get everything started while we were already here. We said we thought it could be arranged if they could do everything tomorrow. So his staff began to see if they could get all the necessary tests scheduled for the next day, while I called The Corporate Angel Network to switch our flight, and the hotel to see if we could stay another night. They got everything scheduled and so did we. I called my mom and asked if she minded to stay another day-it was fine. 

Before we left the hospital they needed to do a finger stick to collect a little blood to check his counts. Then he had to have a chest X-ray to look at his Hickman catheter. This protocol has to be done since Todd's Hickman was not put-in by Memorial Sloan Kettering. They have to ensure that it was done right and looked good before they are allowed to draw blood from it. 

It was rush hour when we left. We walked back to the hotel and Todd put on his PJs and took a nap. I eventually joined him. We napped until about 9:00 pm. We were too tired to go out so we ordered a true New York style Margherita pizza and had it delivered to our room. It was delicious. We watched a bit of TV and I flushed his lines and worked on the blog. We were looking forward to sleeping in, getting a hot shower, and getting a good breakfast since we didn't need to be at the hospital until 12:00 noon. 

In closing, We were sad to hear that our hopes for a curative second transplant were confirmed: not to pursue it because the rate of success would be very low. We were encouraged that we could start the process of getting enrolled so soon. Although the drug is not considered curative, we have hope that Todd will see an improvement in his counts and hopefully have more energy, and a better quality of life. There is still so much they don't know about the sustainability of the drug, or how long it will work, but we feel this is the best option for now. There is always hope that it will work for a long time, or long enough until another cure or newer treatment becomes available. 

I keep telling myself that miracles happen everyday!  It could happen for Todd. Thanks for your continued prayer and support. God is still in control of the big picture. 

Week in Review: Struggling to stay well

It's been a long week for Todd and I. We started off on Monday, March 16, 2015 with blood work and visit with the local oncologist. Todd's hemoglobin was below 8 so they arranged for him to get his transfusion at the advanced treatment area at Miami Valley hospital at 12:45 pm. Our nurse was great and she did her best to get us out by 6:30-7:00 pm.

The doctor asked about checking Todd's iron levels, because iron can build up in the organs after numerous blood transfusions causing damage. He normally treats iron build-up with oral chelation therapy. I told him what his BMT doctor told us: no they don't check iron levels nor treat high levels with chelation therapy because it was "controversial" in its effectiveness. The local oncologist was surprised to hear this. I explained that I think they thought it was mostly a secondary issue that was small in comparison to transplant problems. I did come across a great a talk given by Dr Azra Raza. DR Raza, Video 2. This video is the most comphrensive, but the other 3 are very short and also informative. I'm convinced enough to ask more about it and request his iron levels be checked.

The next morning, Tuesday,Todd didn't look or feel as good as he normally does after a transfusion. He had no pink color and no energy. I called off work the day before not knowing how he would be feeling. He got up and took a shower. I was in the kitchen with our eldest daughter home for spring break when I heard something fall. I yelled out if he was ok and when I didn't hear anything, I went running into the bathroom and found him laying on a towel outside the shower. I asked if he had fallen, but he said no, that he caught himself when he got light headed and tried to lay down on the floor before he did fall. I covered him up and started to dry him off with the towel and helped him into a chair. We got him dry and dressed and back into bed. It was so scary. He got up later and finished shaving but by that evening he still didn't feel well. 

I called the Dayton Cancer Center who had clinic after-care hours around 6:00 pm. They suggested we run him in to see the doctor on call. He wasn't running a fever at the time, but his blood pressure was 114/60. We went in and saw one of his oncologist's associates. They checked his blood counts and found the counts were about the same as Monday. So, he didn't need a transfusion but the doctor could tell he looked pale. He asked how Todd got MDS; he said he was technically too young to have it! That he must have been exposed to something. He asked if he played a lot of golf, because some golfers exposed to chemicals on the green could be affected. He said no. He worked long hours for most of his career and didn't have time for much golf. He asked if he had ever smoked, because they know for sure that Benzene exposure found in cigarettes and exposure to cigarette smoke or gas products can bring on MDS and AML. Todd never smoked and didn't think he was exposed to cigarette smoke overly.  This question is a rabbit hole that Todd finds irritating now. He doesn't know what would have caused the MDS, just like the doctors.  I had known benzene exposure was an environmental cause, but we never could find any relation. He finds this question annoying now.  Someone, somewhere has to be exploring the correlations and causes. Sounds like a good research study: to enroll people with MDS and AML, especially those with the IDH1 and IDH2 mutations, in a study where environmental exposures could be polled. Benzene can be measured in the blood stream but must be done shortly after exposure. Some kind of correlation may be established. Todd worked in the automobile industry along with two other patients we met while at Cleveland Clinic; one was a mechanic and the other was a general manager of a dealership. We were wondering if there was any correlation there, but one was a smoker, so it is hard to say.  Just thoughts...

They ended up giving him IV fluids the next morning, Wednesday, and sent him home. 

He was supposed to go to Cleveland Clinic for treatment and to see his BMT doctor on Friday, March 20, but after we got up at 5:00 am, he just didn't feel like it. I called and cancelled his appointments and we went into the Dayton Cancer Center instead   They ran a CBC and his hemoglobin was above the threshold so we went home. 

By Friday night, he still wasn't feeling well. So, I took his temperature and noticed it was previously 101.9. I was irate. I asked him when he had this fever and why he didn't tell me!  He laughed at me as I stuck the thermometer back into his mouth. We didn't have any Tylenol in the house, so he took an Excedrin Migraine tablet instead without telling me! He was still running a slight fever of 100.6. So I warned him how serious this was and he agreed. So I kept an eye on him and we agreed that since he had a sustained low grade fever for over 24 hours, that we would get up in the morning and go to the ER. 

When I called the doctor's office regarding his fever, they told us that they were open today for the Come Home Clinic and got us into them Cancer Center at 12:15 to run the blood cultures and urinalysis and see the doctor on call instead of having to go to the ER. We were relieved. After collecting the samples and cultures we saw a different oncologist in the practice. His fever was at normal then, but since his white counts were so low, they decided to put him on additional antibiotics: 7 days of IV antibiotics (Vancomycin), oral antibiotics and IV fluids. He slept most of the day Saturday and went back in on Sunday for the IVs. I wondered why they didn't put him on an anti-fungal instead, which is the standard drug additions from what I've read. http://www.uptodate.com/contents/treatment-of-neutropenic-fever-syndromes-in-adults-with-hematologic-malignancies-and-hematopoietic-stem-cell-transplant-recipients-high-risk-patients

Monday, we had the appointment schedule to see Dr Stein at Memorial Sloan Kettering, so he would have to resume The IV treatments after we return. 

AG-221 Trial Study: The Recommended Treatment

First, allow me to apologize for the delay in getting this post written.  At first, we needed time to take everything in.  Second, I began to suffer a severe migraine and ear ache for several days now, and was out for the count.  I couldn't focus on a computer, phone, or any reading the first few days.  I broke down and went to the doctor and got a message on my head, neck, and shoulders.  I am being treated for possibly TMJ (from clenching my jaw in stress) and a possible sinus infection, although the doctor thinks that my symptoms are mainly the result of stress.  (You think!) 

We received a call from Todd's BMT doctor Wednesday evening about 5:30 pm, February 25, 2015.  She called our home phone, which is unusual, and I walked in while Todd was on the phone with her.  He put the call on speaker so I could hear. 

She told me that she had conferred with her colleagues, the other bone marrow transplant doctors, and they came to the consensus that they were NOT in favor of doing a second stem cell transplant at this time.  We were a little shocked, knowing this had been her intent since December, 2014, once Todd's relapse was discovered.  Even now, she did not necessarily "agree" with this choice, but felt she needed to defer to the majority who would rather Todd pursue the trial study for the drug AG-221, because they felt like that would provide the best outcome for Todd, considering the aggressiveness of his disease. 

I knew from my own research, that the success rate for second transplants was not good, but I never wanted to discourage Todd, and after talking to his doctor back in December, we both agreed to be positive and hope for the best; that Todd was NOT a statistic, and that his case has not been textbook MDS from the beginning.  However, this ugly fact had to be considered now when determining his treatment options.

The doctors were not that impressed that his blast counts had been reduced from 7% at the time of relapse to his last biopsy which showed 3% blasts.  Because Todd relapsed within those critical 100 days post-transplant, and that after three rounds of Vidaza,  his disease was still present, they didn't think a second transplant would be successful.  This was devastating news all the same.  For the past three months, we had been pinning our hopes on this second transplant, and now they didn't think it had a good enough chance to work.  I asked why the change in that thinking.  She told us the success rates for second transplants with an aggressive disease was in the "teens."  I somewhat knew this, but had hoped Todd's case would be different.  He is younger and healthier than most of the patients who are in published studies; most are about 60 years old.  These odds are not very good, and they didn't want to set the transplant up for failure.  She said that with his chimerism at 75% of recipient cells (Todd's original bone marrow) and only 25% of his brother's bone marrow left, and with still have disease present (3% blast cells), they would have to do some type of intensive chemotherapy prior to the second transplant to suppress Todd's diseased bone marrow, for there to be any hope of success.  Then, he could get a bad case of Graft versus Host disease on top of the transplant not working, making his overall health condition even worse. 

She said that the only reason they do second transplants, even though the odds of success are so low, is that up until now it has been the only main option, apart from the Donor Lymphocyte Infusion (DLI), which Todd wouldn't be considered for, since his disease is still present (not an aggressive enough treatment).  But, now they have another option: The drug AG-221 in phase 1 trial studies.  The doctors at Cleveland collectively agreed that this drug would be Todd's best chance of controlling his disease.  It would NOT be the "curative" treatment, like the second stem cell transplant, but they have  had success with it controlling the disease and achieving "complete or partial responses."  This is the reason that his doctor was not in favor of the drug versus the transplant, because she said that knowing us so intimately, she wanted to go for the curative treatment. 

Todd asked her if she had been "overruled" by the other doctors in the department, and she said she didn't want to use that word, but that the other doctors were in a position to be much more objective than her.  They all felt it was a better option, to get the most bang for the buck, and help further research in the field, which made us feel like the other doctors just wanted to "guinea pig" Todd by enrolling him in the study.   This didn't sit well with us. The lack of confidence that she had in this decision troubled me.

She encouraged us to get a second opinion and that she would refer us to another physician at another research and BMT hospital.  In addition, they would still consider doing a second transplant at some point, if they could continue to "prove" that he can fight the disease, gaining more time between his last transplant and a future transplant: translation, that he can stay alive long enough and his condition improve enough to justify the second transplant.  Which, they feel is a good possibility if he could start taking the trail study drug: AG-221.  A good number of patients, most 60 years or older, who have not been candidates for a bone marrow transplant have sustained complete or partial responses to the drug since they have been on it.  More about this later.

As to pursuing the study, we would have to wait for the rest of the bone marrow results to come back, which includes cytogenics and the test confirming that Todd still has the gene mutation, IDH2 which is required to be enrolled in the drug study.  After suggesting this study to his doctor a while back, she investigated and found that Todd did have this gene mutation prior to transplant, when he was enrolled in a study with his oncologist at Cleveland Clinic after his diagnosis.  So, the study hospital  needs an official confirmation of this before Todd could be enrolled.  We all agreed that it would do us no good to pursue a second opinion or seek to enroll until we got these results back, which would take another week. 

We also needed to consider where he would enroll in the trial.  The Cleveland Clinic has applied to participate in the study, but it has not yet been approved.  Of course, there a multi-step process that the hospital must go through to obtain this approval.  She said it could take a month, or even longer to get this approval.  In light of this, she suggested that Todd could do another round of Vidaza, to keep his blast counts down, and then revisit the status afterwards.  The only problem with this, they still may not have the approval by then, which would put us in the same situation we are in now.  The closest hospitals that are enrolling patients are in Chicago and Nashville (Vanderbilt), both about six hours away.  We would not be required to stay during the entire trial, but we would have to return for tests at designated points in the study. 

Cleveland would obviously be closer at 3-4 hours away, but I hate to think about delaying treatment for another month or more with Todd's low counts, low energy levels, susceptibility to infections, and requiring blood transfusions every week. 

Concluding the conversation, this was the plan:
1.  Wait until next week, when all the test results were in, including the genetic test confirming the IDH2 gene mutation.  Without this confirmation, Todd would not be eligible for the study at all.  Then would have to go for the second transplant.
2.  If the results show he still has the IDH2 mutation, we will be seeking a second opinion at Vanderbilt Hospital in Nashville.  The BMT doctor will refer us to a doctor there.  We decided if we were going to get a second opinion, that we might as well have it done at a place where they are currently conducting the trial drug study, so that we could get feedback about how well it has been working.  If I had the money to fly often, I would rather go to Memorial Sloan Kettering in New York where the lead doctor and investigator, Dr. Eytan Stein is at.  He has been working with the drug the most.

So, with all this thrown at us in a matter of minutes, we were overwhelmed, sad, and heart broken.

We kept discussing the conversation that evening, questioning their recommendation.  We refuse to allow Todd to be a guinea pig.  I got up the next morning and decided that WE were going to make the final decision about what treatment he would do.  If we wanted to go for the second transplant, we would tell them that was our choice, and if they refused to do it, then we would go somewhere else.  

Still feeling like I needed more information about this decision, I began a further investigation into the drug and the trial study.  I'm so glad I did. 

About the Drug
The drug AG-221, is a pill that is taken over the course of 28 days per cycle.  Tests to check progress would include bone marrow biopsies, blood work, liver tests, etc.  After talking to the doctor that night, I was under the impression that the drug would work similarly to Vidaza, in regards to still producing low blood counts, but after further research, I don't believe that this is the case. 

After going on various websites, I found where Dr. Stein had presented his findings at the most recent ASH convention in December, 2014 on the drug company's website (Agios).  When I heard him say that patients taking the drug were responding in as little as one cycle, and that their blood counts had come up while blast counts had been reduced, I jumped for joy.  He cites one case where a patient's blast counts had gone done from 44% to 12%; Hemoglobin increased from 10.9 to 11.2; Platelets increased from 29,000 to 106,000; and ANCs went from .1 to 1.3!  (Stein, 2014, slide 28).  He even goes on to explain that even partial responses had to have platelets over 100,000 for it to be considered a partial response. This is so much better than what Todd is living with now (Platelets running 10,000-25,000)!    Here is the link if you are interested in this brief presentation.  Start at slide 18 and end at slide 29.  It does take a Shockware plug-in I believe to watch, but it shouldn't be an issue for most.
http://edge.media-server.com/m/p/s4b9a35f/lan/en

Key information: 

• Patients even on the lowest doses have received some response. Many have had relapse of their disease after a bone marrow transplant. 
• This Phase of the trial is to help determine the amount of the drug patients can take with minimal toxicity and still receive a response.  So, Todd would receive increased doses over time to "help determine the MTD or maximum tolerated dose and/or the recommended Phase II dose."  (U.S. National Institutes of Health. Purpose. 2015)  Retrieved from: 
  https://www.clinicaltrials.gov/ct2/show/NCT01915498?term=AG221&rank=3
• We are guaranteed certain rights, like they have to tell us which amount he will be given, he can stop or quit the study at anytime, and if they prove that a certain amount is the most beneficial, they can stop the trial and give him the appropriate amount.  (Memorial Sloan Cancer Center, 2015)  Retrieved from: http://www.mskcc.org/print/cancer-care/clinical-trials/how-decide-whether-clinical-trial-right-you  They have yet to reach a maximum tolerated dose yet. 
• The drug company runs the study at the designated hospital, under the care of a primary investigator (doctor) and co-investigators (other doctors), which can be a bit scary, but on the positive side, all of the costs of the drug, tests, and hospital expenses are paid by the drug company.   
• The job of the drug is to block the enzyme that allows the cells to mutate.  Therefore, it allows a good number of the blood cells to mature to healthy functioning cells. Thus, higher blood counts and lower blast counts.  Here is another great article that features information from Dr Stein.  http://www.targetedonc.com/conference/ash-2014/ag-221-sparks-durable-remissions-in-idh2-mutated-aml/2

 Of course, with any study, there are bad results too.  There have been some that have died from disease progression, or other causes and some that have not had any response.  But, a majority have done well.  With every treatment comes risks, but also the hope of remission.

In conclusion:

At this point, the only other step to the above discussed treatment plan, would be another addition:

3.  If the second opinion is the same, to pursue the trial drug study, then I think we will likely enroll soon thereafter at Vanderbilt, instead of waiting for the Cleveland Clinic to get approved.

Of course, all this is subject to change, in light of further information.

Thanks for your patience in waiting for me to get this posted and for the length of the post.  I will give another update when we have further information.  In the meantime, I expect that Todd will need another transfusion before Wednesday of this week.

We covet your prayers and support,
Kimberley

Other information about AG-221:
On YouTube:
https://www.youtube.com/watch?v=Pnkr2gZfr64

http://ashclinicalnews.org/trial-roundup-december-2014/

http://www.agios.com/pipeline-idh.php

http://investor.agios.com/phoenix.zhtml?c=251862&p=irol-newsArticle&ID=1916041&highlight=