Cycle 1 of NIH Ibrutinib (PCI-32765) clinical trial

07-17-2012 Leukemia Update

La Verne Abe Harris, Ph.D.

If any of you have read the novel by Mary Shelley (1818) or watched the horror film Frankenstein (1931) with Boris Karloff, you are well acquainted with the most famous line of the story, “It’s alive! It’s alive! It’s alive!” (http://www.youtube.com/watch?v=xos2MnVxe-c). That is how I felt after returning from the National Institutes of Health (NIH) in Bethesda, Maryland this week. LOL.

The day after Carl and I arrived, I had my blood work done (12 tubes of blood) and a meeting with Dr. Mohamed Farooqui, Dr. Saba (a research fellow), and a medical student. The only meds I am on prior to the clinical study are herbal supplements, which have been approved by Dr. Farooqui.

Cycle 1, Day 1: July 12, 2012

I had a rough night on Wednesday, July 11. I am not sure if it was nerves or that I was being tested again. I went to bed with the start of vertigo, which entails dizziness and nausea. It lasted off and on all night long. I did get a little sleep. Luckily it was not the full-blown vertigo I have had before from Meniere’s Disease, which feels like seasickness lasting eight hours. Carl was concerned that my lymph node biopsy would be cancelled. It was not, since I was able to hold myself together for the procedure. That is, until the nurse asked me to sit up from the surgical bed and I was visibly dizzy. They wheeled me into the hospital on a bed and I felt pretty pampered. I got through the lymph node biopsy in my right under arm with local anesthesia and a discussion of politics with Dr. Chang’s team. He said I would probably be in pain afterwards, but I was not and did not even need a Tylenol. I did not have pain during the procedure, which he found unusual.

Carl was my drug dealer for the day and picked up the following prescriptions:

Acyclovir (800 mg, 2X/day) to prevent Zoster infections (shingles) in the middle of the study.

Allopurinol (300 mg, 1X/day) for 14 days to prevent tumor lysis syndrome (TLS).

When a person with leukemia is treated with chemotherapy, the content of CLL cells is destroyed and the toxic content of the cells go into your blood and can hurt your liver and kidney. Alloprurinol is a drug that is used to prevent this from happening. Ibrutinib (PCI-32765) is not known to give leukemia patients TLS; however, allopurinol is given as a precautionary measure.

Ibrutinib (PCI-32765): Take three tablets a day (420 mg total) alone (so that it can be properly absorbed) for as long as it works. This drug has been tested in clinical trials for only 11 months. Ibrutinib, a kinase inhibitor, disrupts the signaling pathways of B-cells and pushes them out of swollen lymph nodes, and hiding places in the spleen, etc. Scientists do not know the adverse effects of long-term usage.

I need to return to NIH every two weeks this summer, then every month, and then every three months after the first of the year. No naprocin or aspirin. No alcohol intake the first month because it may raise the concentration of the drug in my liver.

I took the first treatment Thursday with no side effects. I did manage to sleep three hours in the afternoon, but I think that was warranted after all my body had been through.

Cycle 1, Day 2: July 13, 2012

Eight tubes of blood were taken from me. After one day, my white blood count (WBC) increased 1,000, which is less than expected. My platelets were decreased 27K, which was expected. Every patient is different.

My second lymph node biopsy was done by Dr. Brad Wood. Six samples were taken from the same node under my right arm. One sample will be sent off in formalin and the other five will be taken in saline. They will be studying the tissue samples separately.

Side effects:

1. Five people in the study have had bleeding of the brain resulting in one death. These participants were on a blood thinner called Coumadin. My patient advocate Dr. Chaya Venkat advises eliminating blood thinners, such as fish oil from my herbal supplements.

2. Because of the potential side effect of internal bleeding, I need to watch out for excessive bruising and rashes. Bruising may mean my platelet count is too low.

3. Rashes may indicate I am allergic to the experimental drug. Benedril should help with the rash temporarily.

4. Participants have also complained of muscle and joint pain and diarrhea.

5. Dr. Farooqui warned me that several patients have had a strong reaction to mosquito bites. That is not new to me, since my mother always said I had “sweet blood” when the mosquitoes attacked me. Glad I am not in Houston. I will heed the warning.

6. Leg cramps are another side effect. Dr. Farooqui said to take electrolytes, water, massage the legs, and take one teaspoon of mustard. I asked him if Dijon mustard counted. He chuckled.

Emergency situations:

1. If I begin to suffer extreme fatigue or have lots of bruising, it is an indication that my platelets may be low (<100K) and my hemoglobin levels may be too low (<11.0). It may also indicate internal bleeding. I may need a transfusion at this point and I am supposed to go to the hospital immediately.

2. If my neutrophils are less than 500 (0.5), then I am at risk. This usually comes with a fever and is a medical emergency.

3. Evidence of a rash may indicate that I am allergic to Ibrutinib.

In Conclusion

I am B22 (the second cohort of 17p deleted patients), and No. 41 overall (out of 64). Two of the Ibrutinib clinical studies in the U.S. have closed, and the NIH study will close this fall. I consider myself lucky.

All we have in this thing called life is what happens in the here-and-now. Being stuck living in the past or living in the future is a waste of your beautiful life.

We have to determine what risks in life we are willing to take, and weigh the benefits to the losses. This also applies to the people in our lives. Dump the toxic people and surround yourself with people who make you happy.

Dr. Brian Koffman, who is a medical doctor with leukemia, says, “ There is a cost to doing anything. There is also a cost to doing nothing.”