More Good Results from CAL-101

Today was the day we have been waiting for. Marian's white count finally dropped significantly after eight weeks of CAL-101 in combination with Rituxan. The Rituxan infusions are behind her now and, as of today, so are the weekly office visits. For the month of December, she will return every other week. But after December 30, she will only have to go once every four weeks. She can get on with her life.

As I've explained in previous posts, CLL behaves differently in every patient. Because the blood, the bone marrow and the lymphatic system are all interconnected, any disease originating in one of these will also affect the other two. Leukemias are cancers of the white blood cells. CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by producing antibodies. In CLL, the DNA of a B cell is damaged, so that it cannot produce antibodies. Additionally, B cells grow out of control and accumulate in the bone marrow and blood, where they crowd out healthy blood cells. In some CLL patients, the disease proliferates more in the lymph nodes than the blood and marrow.

Even though Marian and John have familial CLL (just like other forms of cancer, CLL can be inherited genetically), their diseases are not identical. Marian's CLL has progressed primarily in her blood and marrow. She needed treatment because her platelets were steadily declining and she was becoming anemic. John's CLL has always progressed in his lymph nodes. His WBC was moderately high, but his other counts were fine. However, his lymph nodes swelled so large that they caused pain. Marian has had some lymph node enlargement, but nothing like John's. John has minimal bone marrow involvement, while Marian's marrow showed 90% CLL infiltration at the start of treatment. Their prognostic indicators are different as well. Marian is mutated (good). John is unmutated (not good). Marian has the 11q chromosomal deletion (not good). John has the 13q chromosomal deletion (good).

The treatments John had prior to CAL-101 reduced his white count, but did not successfully clear his lymph nodes of the CLL. And his lymph nodes were the reason for treatment. Even chemotherapy (FCR) had very little effect on his nodes. Within two months of his last round of FCR, they were already growing again. It was very disappointing and scary. It was looking like stem cell transplant might be our only option. And in order to succeed with a transplant, the patient has to first achieve a complete remission. FCR is usually the treatment used to get that remission and although I knew there were other options, I was feeling pretty discouraged. To fail FCR the first time you use it is not good. Not good at all. I will never forget the day Dr. Flinn looked at us very somberly and said, "This is serious. This isn't good." It was a very hard day.

I had heard about CAL-101 through online friends. But I knew it was very new and unproven. The trials were just getting underway. (CAL-101 is an isoform-selective inhibitor of PI3Kδ that inhibits PI3K signaling and induces apoptosis of CLL cells in vitro). I knew one patient who was getting great results in a clinical trial with Dr. Byrd. He also had the lymph node issues and they were responding impressively. So I started checking into clinical trials (searching online) and where they were available in the hope of avoiding transplant. I knew that Dr. Flinn had trials open using CAL-101 in combination with other therapies. But I was not aware that he was participating in a clinical trial with CAL-101 as single agent. I didn't see one listed online and we were between office visits.

Although I am not a doctor, I am a very educated caregiver. And I personally believed John would be best served by CAL-101 as single agent. (I didn't want him to take more chemo and I didn't want him to take more Rituxan because he'd already had it twice without success.) I remember going to see Dr. Flinn at our next visit and telling him that I had made an appt. for John to see Dr. Byrd in Ohio because he had a clinical trial open with CAL-101 as single agent. Dr. Flinn smiled and said, "I'm participating in the same trial." It was a huge relief to know we would not have to travel. But I would never consider choosing convenience over the best option for treatment. (And if John disagreed with me, this would be something I would be willing to fight about. LOL.)

John began CAL-101 as single agent at the lowest dose (50 mg.) on May 27. Right after he was accepted into this study, it was closed to new patients. But other combination therapy trials opened. And one of them was CAL-101 in combination with Rituxan for elderly, previously untreated patients. (The older I get, the more I dislike the word elderly. My mother-in-law feels the same way.)

In most CLL patients, CAL-101 clears lymph nodes amazingly fast, but initially raises an already elevated white count before it lowers it. That can be a problem, and is one reason CAL-101 is being studied in combination with other drugs. The goal is to blunt the rise caused by CAL-101 with another drug that is already known to lower the white count.

This is just one example of why the same therapy is not right for every patient. And this is another example of the variations between patients even with familial CLL. John was the odd patient who did not experience a rise in his white count at all. And his lymph nodes began to shrink within two days of taking his first dose of CAL-101. After six months of CAL-101, his counts are stable (all within normal range) and the nodes are still shrinking. John says he can still feel a few of them if he presses on certain areas, but they feel smaller and none of them are visible at this point (which makes him very happy because he hated his swollen neck). I don't know if every node will ultimately be reduced to normal size. But we will be very content just to keep the disease under control.

Marian has been the more typical patient when it comes to the rise in WBC. Before beginning treatment, her highest white count was 53.8. Her highest white count after treatment began was 74.7. And that was at the end of the first week. Dr. Flinn said today that without the Rituxan, it probably would have gone higher. Last week her WBC was still 62.7. But today it was 50.7. Dr. Flinn said that the white count usually starts to improve at about eight weeks. So she is right on schedule. She has completed the eight weeks of Rituxan infusions, so from here on she will be on successive 28-day cycles of CAL-101. Today she began Cycle Three. Although the trial is for a total of twelve cycles, patients who continue to respond will just continue taking it indefinitely (as long as it works for them).

Based on the results so far, I believe CAL-101 will ultimately be approved by the FDA for CLL. But one of the great things about being in a clinical trial is that the drug will not be taken away from anyone who is responding to it even if it doesn't get approved. Some people fear clinical trials for some reason and associate them with being a medical guinea pig. Because of all the reading I have done, I don't feel that way at all. I am very thankful that John and Marian both have had the opportunity to be involved in these trials. They are getting cutting edge treatment that is not available everywhere. In John's case, the "gold standard" treatment did not work. I don't even like to think about what we would be going through right now had CAL-101 not been an option for him.

If you read my blog regularly, you have read some of these background details before. But I know that people searching CLL on the Internet often visit my blog -- maybe only once -- and I sometimes go over certain details more than once for the benefit of someone who isn't reading every post. There is a lot of interest in CAL-101 right now -- for good reason -- and I like sharing our experience with others who are seeking information. I knew to ask about CAL-101 because of online CLL friends who shared their experience with it. Actually, it was one specific online friend and his results that gave me hope before I even asked Dr. Flinn about it. (Thank you, Randy!)

I would encourage anyone considering treatment right now (especially if you have stubborn lymph nodes) to investigate the possibility of enrolling in a clinical trial with CAL-101. Medical insurance will often cover doctors and hospitals in other parts of the country and sometimes even travel costs. If traveling to a specialist is an option for you, I would strongly urge you not to choose convenience over an expert opinion and the highest level of knowledge and experience with this disease. It does make a difference, I promise you. And in some cases you can consult a specialist and then have him or her work in conjunction with your local oncologist for treatments that are available locally. Thoroughly investigate all of your options. You won't regret it.

Also, if you have any questions you would prefer to ask privately rather than post a comment, please feel free to email me at


Unknown said…
Great news and results for Marian and John. Praise God for Cal 101.
Deb Light said…
Hi Shari,

Thanks for being so detailed because I know it helps the new Cll patients and refreshes the others of us memories.
I am so glad Marian and John are doing so well on Cal-101.FCR worked for me.It has been 4 years now and still a pretty good remission.Wow,God is good.
Did you mean Marian is mutated instead of unmutated?
Glad to hear some good news today.It lifted my spirits!

Love Ya,
Shari said…
Yes, Deb. Marian is mutated. Ooops. Thanks for catching my typo. I will go back and fix it now. LOL.

Thanks for reading the details, Anita. You know how thankful I am for CAL-101.
Shari said…
Oh, and Deb, I meant to say that I am so thankful you are still in remission after four years! Yes, God is good. I'm glad you added your results because so many do get good remissions from FCR and it's important for patients who are reading to know that.

Love you too!
justme said…
Thanks for this update, Shari. It's great to read of the good results John and Marian continue to experience with Cal-101. WooHoo!