CAL-101: New Generation of Kinase Inhibitors
When Rituxan made its debut about a decade ago, this immunotherapy drug revolutionized the treatment of CLL. Addition of this monoclonal antibody to existing standard chemotherapy drug regimens improved response rates as well as duration of remissions in majority of patients. The good thing about chemo-immunotherapy combinations (FCR is a famous example of such a combination) is that the addition of the immunotherapy component did not add significantly to the toxicity of the regimen, and at the same time it made significant improvements on the response side. Better results, with no increase in toxicity – that is what I like to hear.
Now we can hope for the next breakthrough, the next phase of targeted and designer made drugs. I am sure most of you have heard of Gleevec, the drug that changed the playing field entirely for CML patients. It gave hope and life to CML patients who had none before. True, it fell a tad short of full and no-looking-back cure of CML. Patients do develop resistance to it over time, and certain percentage of patients relapse even while on the drug. But the impact it has had on CML treatment is nevertheless stunning, to say the least. Building on success, new and better versions of Gleevec style drugs are already in the works.
Gleevec and CAL-101 belong a group of drugs called kinase inhibitors. We discussed the science of kinase inhibitors (cartoon version, I am afraid), in an earlier article. The science has not gotten any easier to explain and understand since I wrote that last article. I therefore suggest you refer to it to refresh your memory of how CAL-101 works.
For now, as a quick heads-up, let us remember CAL-101 is an orally available drug. You pop a pill, once or twice a day depending on the dose and schedule, and that is it. No trips to the back room of the oncologist’s office for a long and tedious infusion, no nasty needle pokes while they try to find a good vein. It seems to be relatively well tolerated. We have no idea how much it will cost, when (if) it is a fully FDA approved drug and available for the general patient. Right now, it is only available to patients participating in registered clinical trials. Call me a cynic, but something tells me this is not going to be a cheap drug, once it does become available.
CAL-101 seems to mess with CLL cells ability to congregate in cozy little groups in lymph nodes, spleen etc. It has become increasingly clear that CLL cells are a lot harder to kill when they are nicely tucked away among their fellow cancer cells and other sympathetic “nurse-like cells” giving them encouraging survival signals – telling the cancer cells to live long and prosper, as it were.
Most drugs available to us are able to clear CLL cells floating around in open blood circulation pretty easily. Blood counts are the first to recover. Sky high WBC and ALC take a nose dive downwards pretty soon after start of most therapies. But clearing bulky lymph nodes, that is an entirely different matter and much harder to do. Some drugs are terrible at it – for example, Campath is contra-indicated for patient with bulky nodes since it does such a poor job of clearing them.
This seems to be where kinase inhibitors such as CAL-101 have their most impact. Kinase inhibitors such as CAL-101 seem to be able to drive the CLL cells out of their lymph node locations and out into open blood circulation, where they are then easily killed. A consequence of this mechanism of action is that soon after start of therapy with CAL-101, there is a very satisfactory melting away of bulky nodes, and this is paralleled by increased numbers of CLL cells in the blood counts. All those CLL cells flushed out of the lymph nodes and spleen have to go somewhere, and that is why your WBC and ALC may shoot up immediately after start of therapy. But this should not alarm people who understand the mechanism. Given a little time, the lonely CLL cells cruising around in the blood are easily picked off, one at a time. Blood counts soon normalize, along with continued reduction in lymph node size.
OK, with that quick primer on how CAL-101 works, it is time to review the latest clinical trial results published at ASH 2010 conference.
Abstract 55: CAL-101, An Isoform-Selective Inhibitor of Phosphatidylinositol 3-Kinase P110, Demonstrates Clinical Activity and Pharmacodynamic Effects In Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia
Richard R. Furman, MD1, John C. Byrd, MD2, Jennifer R Brown, MD, PhD3, Steven E. Coutre, MD4, Don M Benson, Jr., MD5, Nina D. Wagner-Johnston6, Ian W. Flinn, MD, PhD7, Brad S. Kahl, MD8, Stephen E. Spurgeon, MD9, Brian Lannutti, PhD10, Neil A. Giese, Ph.D.*,10, Heather K Webb, Ph.D.*,11, Roger G Ulrich, Ph.D.10, Sissy Peterman*,12, Leanne M. Holes*,10 and Albert S Yu, MD*,10
1 Weill Medical College of Cornell University, New York, NY, USA,
2 The Ohio State University, Columbus, OH, USA,
3 Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA, USA,
4 Stanford University School of Medicine, Stanford, CA,
5 The Ohio State University Medical Center, Columbus, OH, USA,
6 Washington University, Saint Louis, MO, USA,
7 Oncology, Sarah Cannon Research Institute, Nashville, TN, USA,
8 University of Wisconsin, Madison, WI, USA,
9 Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland, OR, USA,
10 Calistoga Pharmaceuticals, Seattle, WA, USA,
11 Drug Safety, Calistoga Pharmaceuticals, Seattle, WA, USA,
12 Clinical, Calistoga Pharmaceuticals, Seattle, WA, USA
Introduction: The class I phosphatidylinositol 3-kinases (PI3Ks) regulate cellular functions relevant to oncogenesis. Expression of the PI3K p110 isoform (PI3K) is restricted to cells of hematopoietic origin where it plays a key role in B cell proliferation and survival. In chronic lymphocytic leukemia (CLL) the PI3K pathway is constitutively activated and dependent on PI3K. CAL-101 is an isoform-selective inhibitor of PI3K (EC50 of 62 nM in a whole-blood assay with >200-fold selectivity relative to other PI3K isoforms) that inhibits PI3K signaling and induces apoptosis of CLL cells in vitro.
Methods and Patients: This Phase 1 study evaluated the safety, pharmacokinetics, pharmacodynamics and clinical activity of CAL-101 in patients with relapsed or refractory hematologic malignancies. Sequential cohorts of patients were enrolled at progressively higher dose levels with cohort expansion based on toxicity profile and plasma exposure. CAL-101 was administered orally one or 2 times per day (QD or BID) continuously for 28-day cycles for up to 12 cycles (with the potential for more prolonged therapy on an extension protocol thereafter). Clinical response was evaluated according to standard criteria.
Results: At data cutoff, the study had enrolled 37 patients with CLL. Patients included: males/females n=31 (84%)/6 (16%) with median age of 65 [range 37–82] years, refractory/relapsed disease n=24 (65%)/13 (35%), bulky disease n= 29 (81%), and adverse cytogenetics of del(17p), del(11q) or both n=22 (63%). The median number of prior therapies was 5 [range 2–14]. The number (%) of patients with specific prior therapies included: rituximab n=37 (100%), purine analog n=37 (100%), alkylating agent n= 31 (84%), and alemtuzumab n=12 (32%). CAL-101 dose levels were 50 mg BID (n=1), 100 mg BID (n=4), 150 mg BID (n=11), 200 mg BID (n=10), 350 mg BID (n=7) and 300 mg QD (n=4). The median number of treatment cycles was 9 [range 1–13], with 21 (57%) patients continuing on treatment (11 on study and 10 on the extension protocol after 12 cycles). Symptomatic adverse events were infrequent, usually low-grade, and not clearly CAL-101-related. Grade 3 pneumonias occurred in 9 (24%) patients. Grade 3 hematological laboratory abnormalities included neutropenia n=9 (24%), thrombocytopenia n=4 (11%) and anemia n=3 (8%) that were not usually considered CAL-101-related. A pharmacokinetic analysis of dose-proportionality showed minimal increases in plasma Cmax and AUC at CAL-101 doses >150 mg BID; these data, taken together with the tumor regression results, have proved helpful in supporting Phase 2–3 dose selection. Flow cytometry of CLL cells from patients showed that CAL-101 reduced constitutive expression of phospho-AKT to background levels when measured after 1 week of treatment (p<0.0001), demonstrating pharmacodynamic inhibition of activated PI3K signaling. Plasma concentrations of chemokines CCL3, CCL4, and CXCL13 were elevated at baseline and decreased significantly within 1 cycle of CAL-101 administration (p<0.001 for all comparisons). CAL-101 reduced lymphadenopathy in all 32 (100%) patients with at least 1 post-treatment tumor assessment; 29/32 (91%) achieved a lymph node response (50% reduction in target nodal lesions). An initial increase in peripheral absolute lymphocyte counts of >50% from baseline was observed in 21/35 (60%) patients; increases were maximal during the first 2 cycles and decreased thereafter; the pattern suggested drug-mediated lymphocyte redistribution. Considering nodal and peripheral blood changes together, partial responses were observed in 11/33 (33%) of patients. The median duration of response had not been reached; 7 patients had response durations of 6 months. Of 20 patients with CLL-related thrombocytopenia (baseline platelet counts <100,000/µ L), 15 (75%) had either an improvement to >100,000/µ L or a >50% increase from baseline.
Conclusions: CAL-101, an oral PI3K isoform-selective inhibitor, shows acceptable toxicity, positive pharmacodynamic effects, and favorable clinical activity in heavily pretreated patients with CLL, including patients with refractory disease, bulky lymphadenopathy, and poor-prognosis cytogenetics. The high level of lymph node regression and prolonged duration of symptomatic tumor control strongly support evaluation of CAL-101 alone and in combination with other chemo/immunotherapy approaches to CLL management.
Disclosures: Byrd: Calistoga Pharmaceuticals: Consultancy, Equity Ownership. Brown: Calistoga: Consultancy. Kahl: Calistoga Pharmaceuticals: Consultancy, Research Funding. Lannutti: Calistoga Pharmaceutical Inc.: Employment. Giese: Calistoga Pharmaceuticals: Equity Ownership. Webb: Calistoga Pharmaceuticals: Employment. Ulrich: Calistoga Pharmaceuticals: Employment, Equity Ownership. Peterman: Calistoga Pharmaceuticals: Employment. Holes: Calistoga Pharmaceuticals: Employment. Yu: Calistoga Pharmaceuticals: Employment, Equity Ownership.
Clinical Trial Design, Adverse Effects
This clinical trial recruited 32 previously treated CLL patients. I think it is fair to say, they are a pretty tough crowd to treat. The median age was not all that high (65 years), and it reminds me once again that there is a real disconnect between the average age of clinical trial participants and the average age of CLL patients in general. Pity. It makes it harder to apply the lessons learned in clinical trials to real live patient populations. Almost all of the patients were either refractory or relapsed. (Remember, ‘refractory’ is worse than merely ‘relapsed’). 29 of the 32 patients had bulky disease. 22 of the patients had 17p and / or 11q deletions, the high risk FISH abnormalities we are all aware of by now, I hope.
Drug dosage varied greatly, from as little as 50mg tablets twice daily all the way to 350 mg / twice daily. It looks like the researchers are zeroing in on 150 mg/twice daily as the optimum dose.
I am worried to see the continued observation of pretty serious grade-3 pneumonia in a quarter of the patients.
Since I take patient confidentiality seriously, I am not at liberty to disclose the full details – but I think it is OK to disclose that I have heard from more than a couple of the patients in this trial who came down with pneumonia. Pretty scary stuff. Since the patients take CAL-101 at home, in a couple of the cases that I am aware of the early stages of the pneumonia were not readily noted and treated correctly by local healthcare providers. Confusing matters further, apparently the lungs of the patient sound just fine when physicians listen to them. More often than not, patient is sent home with a prescription for antibiotics, on the assumption the horrid cough is due to bacterial infection of some sort. Not the case at all, it seems. The driving force behind the pneumonia seems to be some sort of drug related lung inflammation. The only thing that seemed to work in the couple of cases I heard from is massive doses of steroids, sooner the better, to reduce the inflammatory process underway.
As I said above, this perspective is purely anecdotal and I am basing it on just a few cases that I heard from. Nevertheless, it is worrisome. I wish the authors of this paper had gone a bit further and gave their opinion as to why fully a quarter of the patients developed high grade pneumonia, rather than just stating the fact of this observation. If you are a participant in CAL-101 trials, this one or others in the future, please be aware that pneumonia is perhaps the single biggest concern as far as adverse effects go. If you develop a bad cough while on the drug, please do not dismiss it lightly. Make sure you get to your clinical trial researcher, not just make-do with local talent that has no clue what is causing the cough. Pneumonia caused by drug related inflammation is very different from the general garden variety pneumonia and needs to be treated differently.
Other adverse effects were grade 3 neutropenia (9 patients), thrombocytopenia (4 patients), anemia (3 patients) – out of the 32 patient cohort.
Results
So, what did this group of high risk, relapsed / refractory patients get for their efforts? As advertised, CAL-101 did indeed shrink lymph nodes in all 32 of the patient volunteers. 29 of them had as much as 50% reduction in their target lymph node. As expected, there was a big spike in WBC in the first couple of weeks, observed in 60% of the patients. But this spike gradually resolved itself and the blood counts normalized nicely thereafter. Overall, 33% of the patients had what is termed “PR” – partial response. Please refer to our earlier article “(Almost) Everything you need to know about CLL” for a clear understanding of what a “PR” response means.
This is how the researchers themselves evaluate the potential importance of CAL-101:
“CAL-101 shows acceptable toxicity. The high level of lymph node regression and prolonged duration of symptomatic tumor control strongly support evaluation of CAL-101 alone and in combination with other chemo/immunotherapy approaches to CLL management.”
Symptomatic tumor control? And quarter of the patients experiencing grade-3 pneumonia is “acceptable toxicity“?
Boy, that is a far cry from a CURE. But let us be reasonable, let us be optimistic. These are early days. In combination with other drugs – wait for it – Rituxan and / or bendamustine – CAL101 may prove to be a much needed drug to better treat high risk patients with bulky lymph nodes. And its impact as a single agent may be much better in lower risk patients who have not been as heavily pre-treated as this lot. It is also important to remember that the single stellar feature of CAL-101, its ability to shrink swollen nodes, is very much a desired feature. And that too in poor prognostic patients with unfavorable FISH cytogenetics. At this point in time we are sorely lacking in drugs that can do it as well as CAL-101 can, and that is not something to sneeze at. But anyone who thought this drug is going to be the slam-dunk CURE we are all hoping for, or walked into the trial expecting to see very few adverse effects – after all, how much harm can a couple of tiny little pills do? – these folks were no doubt disappointed.
This abstract did not thank the patient volunteers who made this study possible – hopefully this oversight was corrected at the actual oral presentation of the research at ASH 2011 conference. In any case, please join me in a heartfelt round of applause for these brave volunteers.
Editorial: Reading the Tea Leaves
Reading research abstracts, understanding the clinical details and almost as important, understanding the details buried between the lines and not quite spelled out – this has to be an art form. I have read thousands of these abstracts and articles in my career as a layperson observer of the CLL scene for the last ten years. I think I have gotten pretty good at it, even if I say so myself.
Credibility is paramount. Results are worth only as much as the credibility of the study that reports them. What makes some papers more credible than others? For starters, the name recognition of the researchers involved, as well as the reputation of their respective organizations. I have highlighted the well known names of some of the authors on this abstract, as well as their institutions. Clearly, this is an important paper with some high powered CLL experts on the author list.
Another aspect of credibility is the disclosure statement at the bottom of the abstract. 10 out of the sixteen authors on this paper had significant financial dealings with Calistoga Pharmaceutical, the company that owns CAL-101. That does not mean automatically that the credibility of the paper is destroyed, lost in a haze of conflict of interest. We cannot afford to be such purists in this day and age, where much of the research funding comes from drug companies. Three of the authors on this paper actually work for Calistoga. Does this invalidate the results? I do not think so. It is important not to throw the baby out with the bath-water, as we follow the money trail. All I am doing is pointing out to you some of the details I pay attention to, as I read and review these articles.
Somethings were left unsaid in this report. No discussion of why they had high grade pneumonia in fully a quarter of the patients. Notice, they did not say this is possibly unrelated to the drug. I would also have liked to see some comment on what they thought was happening in the bone marrow. Yes, CAL101 cleared lymph nodes, swollen spleen. But what about that most crucial and one-of-a-kind organ of hematological health, the bone marrow? We are gently nudged to assume, infer, hope – you name it – that because platelet counts improved, this means that the bone marrow cleared out as well. Perhaps this is indeed the case. Me, I would have liked to seen more direct proof that indeed this was the case. I am not sure the FDA is going to buy the argument either, without bone marrow biopsies to prove it is indeed the case. As I said, read between the lines to get the full flavor of the report.
Disclosure:
Since I discussed the financial disclosures of the authors, it is only fair that I undergo the same scrutiny. For the record and in the interests of full disclosure, I receive no consultancy fees, no research funding, no favors or “gifts” from any drug company. Neither I nor my family have any equity ownership in Calistoga. I have never worked for a drug company and most likely never will. To cut to the chase, I get no money – not a single dime – from anyone other than you, my readers, by means of your donations.
16 comments on "CAL-101: Update at ASH-2010"
Hi, I am the first for once. Were it that this or a very similar drug could attack the darned cells where they hide, and actually make them keel over! I presume that is the holy grail, that would be cure.
This does sound like a good start, and low toxicity, that would be good too. My local haematologist, honest person, who does practice “do no harm”, at least as little as poss whilst having effect on disease as well. I shall show this!
Thanks Chaya, so much. I look forward to the next article.
Mette
the cough……..this is something to really watch! Tom has been on PCI for 13 months and side effects have been tolerable but seem to be revving up a little now that we are past the one year mark. The cough is one. Same scenario that the CAL 101 patient’s had. Terrible, whooping, fatiguing cough treated with Bactrim while being tested for bacteria. Findings showed no bacteria present which means Tom was on major antibiotics for no reason. (sigh)–he still has the cough–going on a month now, but has check up at MD Anderson this Friday. Crackling was heard by ENT here in Austin, thus the Bactrim.
Tom’s blood counts are looking very good and if he had shown no minimal residual disease by Flow, the next test would have been a BMB to see how much CLL was cleared out of the marrow due to PCI treatment. Keating stated that there was no reason for a BMB since Tom’s Flow taken in November 2011 showed MRD. I just wanted you to know that MD Anderson is doing bone marrow biopsies for PCI patient’s who are showing MRD- status by peripheal Flow. That will be interesting to read the results…
Another side effect Tom has had on inhibitor treatment is skin involvement and achy joints–outbreaks on his face which have not been dx yet but have been said to be either CLL or PCI related. Exceptional bruising has been noticed by quite a few patient’s. There is a side effect called by the Houston locals as “The PCI rash”.
Thanks Chaya for all your hard work
Jenny Lou
Thank you Chaya for the great update on Cal101. I often wonder why they don’t also do trials with agents like Cal101 on patients who are previously untreated but soon headed for treatment? The negative side effects seem like they would be minimal and perhaps reduced dosages could hold the CLL at bay for years with such a group. What sound lessons can we learn about Cal101 from a group of patients who have already had round after round of powerful chemo therapy that we know is immunosuppressive and has reeked havoc on the entire blood system? If Cal101 doses are escalated high enough to get results, it doesn’t surprise me that inflammatory pneumonia could result. It seems doubtful to me that agents like Cal101 will ever be the magic “cure” bullet. A low toxic arrow in the quiver judiciously used early to give most CLL patients a 20 year Mexican standoff and reasonable quality of life would be quite an advancement.
Chaya I am wondering if the higher doses of CAL101 are the ones that are resulting in the lung inflammation. I have talked with several people with this reaction and they seem to be the higher doses. Well that is exactly what this study is for, to find out which dose will work the best with least problems. I remember that early in Rituxan trials several people died as a result of the way the treatment was given. So if those of us who have paved the way for CAL 101 are helping on the learning curve, that will be wonderful. I do wish they would publish more information, especially for those of us who are in the trials. The lung problems are very real and very serious, but hopefully they are learning from these and future patients will not have this to contend with. Beth
In answer to Michael, there is an ongoing trial using CAL-101+R for untreated elderly patients. Check out clinicaltrials.gov and trial NCT01203930. The same guys who are doing the trial Chaya has reported on are running this one as well. I considered it at Stanford last January but was told by Dr. Coutre that I was not needing treatment yet. I’d love to hear how this one is going as these are untreated patients AND rituxan is being used as well. But I wish they were making BMB’s part of the before and after view of the drug as I have 80-90% marrow involvement and am looking for front line therapy in 2012. Even if MRD- is not achieved, I’d like to see what happened to the marrow before I sign up.
Another trial for untreated patients will most likely be announced soon by the same wonderful team who bring us the NIH Natural History Study of Untreated CLL Patients. This will be PCI-32765 as a single agent, and I believe it will be open for untreated elderly and for high risk patients of any age. Don’t quote me on that .. I’m going with the rumor mill here. And I don’t know how they will define “high risk”.
All the best .. Lynn in San Francisco
An important correction has been pointed out to me: the abstract reviewed above is from ASH2010, not ASH2011. I have corrected the heading of my review accordingly.
Sorry for this, guys. I don’t usually mess up on details like this – suffice to say I am blushing.
The next article, dealing with CAL-101 in combination with bendamustine and / or Rituxan, WILL be from ASH2011.
Chaya – thank you for another illuminating article. Even though this was from ASH 2010 it was most helpful. I look forward to the next article on CAL-101 in combination with bendamustine and/or Rituxan. All of us w/CLL are hoping that CAL-101 and/or PCI-32765 will be a major advancement in the treatment of CLL.
As someone currently in w/w – I try to learn as much as possible about the various CLL treatment options. There is so much individual variability with CLL I feel it’s best to do my homework before the unpredictable CLL acts up and treatment is required. Here again Chaya, you come riding to our rescue with all your excellent articles.
One of my laments is current cancer patients do not benefit from the same streamlined FDA trial protocols that were used for HIV patients. The process apparently worked well and made life saving HIV drugs available in a much shorter time line.
Chaya, a BIG thank you for another excellent overview.
Regards – Patti
In the CAL-101 trials, the time when the disease moves out of the nodes into the blood stream has been described by some patients as a really unpleasant surge that lasted way too long. Some had to drop out as a consequence. I was dx’d with bulky node CLL in ’98; it resisted 3 cycles of chemo 2000-2002 before relenting to a trial drug in 2003. There were 2 arms: one received the trial drug, the other were assigned both the drug and chemotherapy. I was in the latter group. There was promise of a CR soon after I started and by the end of he trial, it was official. I’ve remained in CR since 2003. The folks given just the trial drug mostly improved but as I recall, none achieved a CR. My point is that as doctors search for drugs to eliminate he need for chemo, meanwhile they’re working on reducing the amount of chemo needed for good results. While I know we all hope for chemo to become obsolete, I’m very grateful I was in the arm that received it. But if the same results could have been achieved with a lot less chemo, that would have been better. -Ellen
Chaya,
Thank you, thank you for this article. I am looking forward to the article re: Bendamustine.
Many Blessings,
Rita
Patti ..
I think the FDA is trying to come to grips with a measure for these new drugs. HIV has an easier paradigm .. reduce the viral load and you have a winner. Not so much with CLL .. We will see what criteria they finally accept for approval. In fact, I wonder if the accelerated approval process will be used, as it was for HIV drugs, with more complete trials following, when it is better ascertained what constitutes “success” in CLL treatment with these new drugs.
Thanks as always to Chaya for being a master navigator in these waters.
Lynn
Chaya,
At the risk of offending someone/everyone, I will “pile on” the issue of disclosure. Two well known hematologists in two different expert locations taught me a trick to determine who are the “real” authors of a paper. Look at both the first name listed on the paper (in this case Richard R. Furman of Weill) and last name listed (Albert S Yu of Calistoga Pharma). Generally, the last named person is responsible for pulling all the data together and putting the paper together. In this instance, if protocol holds, Dr. Yu pulled the paper together. I would be most intereste
Chaya, my apologies to everyone. I failed to complete my statement above. Darn mouse pad! As I was saying, I would be most interested in knowing who actually presented the paper at ASH. One of my two hematologists is uncomfortable with a pharma rep pulling a paper together as he believes they determine what content will be presented. The process of determining what goes into a paper is not democratically determined.
Great paper on your part. As you can tell it struck a responsive chord.
Very informative article, Chaya. The pneumonia sounds scary. Forewarned to watch for the cough and report it to the research people is timely advice. Thank you for your discussion of this.
Chaya, I hope you are enjoying your stay with family in India (I love your country, have been there several times, but now I am leery of international travel…)
This is not the kind of reading I like to do this time of year, but -voila- the content is encouraging. I will continue reading the next one in the ASH series with interest.
Thank you profusely.
My best wishes to you and your family– and to our CLL family— for a healthy and calm new year ahead.
I’m in the CAL-101 trial at MDA. Though it maybe works a little too well sometimes, it works great for me. I got on it because my HMG was trending down over the last 5 years. My HMG went from below 10 to near 14. My bone marrow went from 93% to 22%. My WBC went 45K to 4K. I have been neutropenic a couple of time. Overall I have felt good the whole 5 years, but I feel even better now. So far do good.
I am on the cal 101 trial with rituxan and Leukeran every 28 days. I am mid second cycle. The worst side effect for me is overwhelming diarrhea and cramps. What looked like a 6 month pregnancy (abdomen nodes) and pancake like nodes under my arms have disappeared. It’s an unbelievable change in my body. I can now button my pants and zip my zippers.
If someone has gotten over the diarrhea with a new type of medicine, please do tell.
I have been using Imodium, lomotil, bentyl, welchol and the brat diet but have not been successful.
I am determined to stay on the cal 101 as it has the best potential for me with an 11q and 17p deletion.
Thanks you so much Chaya for all your wonderful reports. Laura Singer
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