Dedicated to Dr. Mohammed Farooqui

This painting is on display at Banner Hospital for the next few months. When it is returned to me, I will give it to Dr. Farooqui as a gift of appreciation.

Novel Antibody Directed at Chronic Lymphocytic Leukemia

By Anna Azvolinsky, PhD¹ | April 3, 2013

¹Freelance Science Writer and Cancer Network Contributor.

Researchers have identified a novel monoclonal antibody directly targeted against a receptor found in abundance on chronic lymphocytic leukemia (CLL) cells, but not normal B cells. The humanized antibody can directly kill CLL cells, according to Thomas Kipps, MD, PhD, professor of medicine and deputy director for research at the University of California, San Diego Moores Cancer Center, and colleagues. The results of the study are published in the online edition of Proceedings of the National Academy of Sciences.

In contrast to normal B cells, CLL cells express a high level of CD44, a cell-surface glycoprotein receptor. CD44 is thought to mediate one of the important survival signals for leukemia cells. CLL cells receive survival signals from its tumor environment, including cells that are present in the lymph nodes and the bone marrow of CLL patients. Previous work from Kipps and colleagues has shown that CLL cells can undergo drug-induced or spontaneous cell death when removed from a patient and cultured in the laboratory. Because the RG7356 antibody induces cell death of the CLL cells by binding to CD44, the drug is a potential new therapy for treatment of at least a subset of CLL patients.

Ibrutinib on a Fast Tract for FDA Approval for 17p Deleted Patients

EXTRA! EXTRA!

April 8, 2013 it was announced that the FDA granted breakthrough therapy designation for ibrutinib (Janssen and Pharmacyclics) as a monotherapy for patients with CLL/SLL (chronic lymphocytic leukemia or small lymphocytic lymphoma) with deletion of the short arm of chromosome 17. This genetic mutation is associated with poor prognosis and is one of the worst prognostic factors in patients with CLL. This is what I have.

This is the third breakthrough designation the FDA granted for ibrutinib an investigational Bruton’s tyrosine kinase inhibitor. One was as a monotherapy for previously treated patients with relapsed or refractory mantle cell lymphoma, and the other was as a monotherapy for patients with Waldenström’s macroglobulinemia.

The breakthrough therapy designation was created in 2012. It enables the development and review of drugs shown in preclinical studies to offer potentially substantial improvements over existing therapies for patients with serious or life-threatening diseases to be expedited.

Patients like me with 17p deletion generally do not respond well to chemoimmunotherapy, and are limited on their treatment options. In my case, because I am bi-racial, I have less than a 1% chance of finding a bone marrow donor match. Ibrutinib has the potential to improve the outcome in this serious and life-threatening disease, and is much less risky than a bone marrow transplant.

A Phase II global study of ibrutinib in patients with CLL deletion 17p, will be available this year and Pharmacyclics plans to enroll 111 patients worldwide. The study called “RESONATE™ -17” is a single-arm, open-label, multi-center trial using ibrutinib as a monotherapy in previously-treated patients who have deletion 17p, who did not respond or who relapsed (a high unmet need population). The purpose of the study will be to determine overall response rate.

Those of you following my blog know that I have just completed my 9-month milestone as “a little white laboratory mouse” in the clinical trial with ibrutinib. Dr. Adrian Wiestner, M.D., PhD, of the National Institutes of Health is the lead investigator in the clinical study. Dr. Wiestner just presented the findings from this clinical trial at the American Association for Cancer Research (AACR) in Washington, D.C. Here is an excerpt from Pharmacyclics’ press release from April 8, 2013. Please note that this is a fast track to FDA approval, and applies to 17p deleted CLL/SLL patients like me. :-)

Phase II Ibrutinib Monotherapy Study Shows CLL Patients Achieved Rapid and Sustainable Disease Control Irrespective of Age or High Risk Prognostic Factor

SUNNYVALE, Calif., April 8, 2013 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq: PCYC) today announced results from a Phase II trial of the investigational oral agent ibrutinib which demonstrated rapid and sustained disease control as a monotherapy in untreated, relapsed and refractory chronic lymphocytic leukemia (CLL) patients, irrespective of characteristics that predict poor outcomes to chemoimmunotherapy.

This study was discussed at today's American Association for Cancer Research (AACR) annual meeting in Washington, DC together in addition to 8 other presentations covering advances in clinical and pre-clinical research with ibrutinib. The Phase II study, which was sponsored by the National Heart, Lung and Blood Institute, included an analysis of two CLL patient cohorts: the elderly, above 65 years of age, (n=24, of which 8 were treatment naive) and the high risk genetic group with a deletion of chromosome 17p (del 17p) (n=29, of which 15 were treatment naive). Many elderly patients with CLL are unable to tolerate aggressive therapies. Patients with deletion of chromosome 17p typically are poor responders to chemoimmunotherapy and have limited treatment options with no standard of care defined. Of all CLL patients enrolled in this trial, 72% had been characterized as Rai stage 3-4, indicating an advance stage, high-risk patient population.

The results of the study were presented by lead investigator Adrian Wiestner, M.D., PhD, Hematology Branch, NHLBI, National Institutes of Health. "Ibrutinib was highly efficacious as a single agent in patients with untreated, relapsed and unresponsive CLL, irrespective of their del 17p status," Dr. Wiestner said. "Responses in this study appear to be durable, and results indicate the drug is effective against the disease in lymph nodes, spleen and bone marrow. This is important because existing therapies often fail to effectively eliminate cancer cells in these tissue sites. Targeted therapy for CLL is becoming a reality, and this new approach may greatly improve the lives of patients with this disease."

The study also evaluated in vivo effects of ibrutinib using blood and tissue samples collected before and during treatment. Ibrutinib demonstrated rapid and sustained disease control in blood, lymph nodes, spleen and bone marrow. After 6 months, 95 percent of patients experienced a reduction in lymph node size and all showed reduction in spleen enlargement, with a median reduction of 55 percent. In 26 patients, for whom a bone marrow biopsy was done, tumor infiltration decreased by 82 percent.

The Progression Free Survival probability for these patients at 12 months was estimated to be 94 percent. Most adverse events were mild and manageable and included diarrhea, fatigue and rash, severe events occurred in less than 13 percent of patients. 

"We are very pleased with the continued research that is being demonstrated at AACR across 9 different presentations. These advances show the potential breadth of the ibrutinib program and provide further opportunities for us to pursue. We are grateful for the continued support of our collaborators, investigators, patients and shareholders," said Bob Duggan, CEO and chairman of the board.

Ibrutinib has been designated as a FDA Breakthrough Therapy in CLL patients with deletion 17p, based on data from completed Phase I/II clinical studies, where ibrutinib as a monotherapy was used to treat patients with this disease. Ibrutinib has the potential to improve the outcome in this serious and life-threatening disease, and may provide a substantial improvement over existing therapies for this indication.

The Ibrutinib story

Forbes Magazine

April 5, 2013

http://www.forbes.com/sites/davidshaywitz/2013/04/05/the-wild-story-behind-a-promising-experimental-cancer-drug/

The Wild Story Behind A Promising Experimental Cancer Drug

Today, Pharmacyclics is a $5.3B company, a value attributable largely to its promising lead compound, ibrutinib, currently in late clinical development for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma, and under investigation for a range of other B-cell malignancies.  A joint development and marketing deal with J&J was announced in late 2011, valued at nearly $1B, including $150M upfront plus significant milestone payments.  Analysts are already pegging future sales in the billions.

Ibrutinib’s emergence as a promising oncology drug – “The Gleevec of CLL,” as one oncologist described it to me – is an almost absurdly improbable story embracing the Human Genome Project on the one hand, and Scientology on the other.

A “Most Wondrous Map”

In 1998, a radically inventive biologist, J. Craig Venter, founded a company called Celera, with the goal of sequencing the human genome within three years.  He was competing against a much larger, well-funded public effort, led by Human Genome Project Director Dr. Francis Collins, who is now Director of the National Institutes of Health.

Both efforts succeeded; the initial draft map of the human genome was famously announced on June 26, 2000 by President Clinton, joined by Venter and Collins.  Clinton said, “Today the world is joining us here in the East Room to celebrate the completion of the first survey of the entire human genome. Without a doubt, this is the most important, most wondrous map ever produced by humankind.”

In 2002, Venter stepped down as President of Celera, and over the next four years, its promise progressively evaporated.  Turning information into value – arguably the key challenge of the genomic era – proved elusive.  The company’s attempts to try its hand at drug development — kick-started by the acquisition of Axys Pharmaceuticals in 2001 — had largely fallen short.  Electing to focus on diagnostic testing, the company unloaded its early stage assets – a phase 1 HDAC inhibitor and a few other preclinical molecules, which in 2006 were picked up for a pittance by a small struggling company called Pharmacyclics.

A Useful Tool

Included among the preclinical assets were small molecules targeting a signal transduction molecule called Bruton’s trysosine kinase – BTK – an enzyme that sits downstream of the B-cell receptor, and was targeted by Celera because of its putative role in autoimmune diseases such as rheumatoid arthritis (a thoughtful discussion of “immunokinase” drug discovery can be found here).  The BTK gene itself — tied through “classical” genetics to the disorder X-linked agammaglobulinemia (XLA) — was first identified in 1993.

As part of their efforts to screen candidate BTK inhibitors, Celera researchers created a “tool compound,” a molecule that would bind BTK permanently (i.e. covalently), and could also be fluorescently labeled.  This tool would help the company identify compounds that could bind BTK tightly, but not covalently, since drug developers traditionally shy away from compounds that permanently bind their target, concerned about their “potential for off-target reactivity,” as a recent review nicely summarizes.  That said, many drugs, both ancient– such as aspirin – and recent – such as clopidogrel (Plavix) and esomeprazole (Nexium) – work through a covalent mechanism.

As Celera researchers pursued BTK inhibitors, they made two important discoveries: first, they learned that their molecules seemed to show activity in arthritis models; second, they progressively appreciated that their tool compound seemed more promising than any of the other molecules emerging from their screens.  It was at this point that Celera’s assets were sold to Pharmacyclics.

Developing Science

Meanwhile, elegant experiments in mice by Harvard immunologist Klaus Rajewsky highlighted the importance of B-cell receptor signaling for B-cell development, stimulating cancer researchers to wonder whether inhibiting B-cell receptor signaling might help treat B-cell cancers.  In rapid succession, scientists from Stanford, Harvard, and other universities reportedly reached out to a small Bay-area biotechnology company called Rigel to request permission to study one of their lead compounds, fostamitinib, an inhibitor of the Syk kinase which is also in the B-cell receptor signal transduction pathway.

The initial results were promising but not stellar, although encouraging responses were seen in some patients, according to Dr. Jeff Sharman, who at the time was a Stanford oncology fellow in the legendary lab of Ronald Levy, and an early proponent of inhibiting B-cell receptor signaling in B-cell cancers.  (In 2010, Rigel partnered fostamitinib with AstraZeneca, and it is currently in late-phase development for rheumatoid arthritis).  Sharman (disclosure: we trained together at MGH) recalls that a frequent visitor to the Levy lab was Dr. Richard Miller, an oncologist and entrepreneur who at the time was CEO of a local drug development company: Pharmacyclics.

Local Hero

Richard Miller was already a bit of a legend in the Bay area; in 1984, he co-founded IDEC with Stanford colleague Levy, UCSD immunologist Ivor Royston, San Diego bioentrepreneur Howard Birndorf, and a trio of top-tier VC investors led by Brook Byers of KPCB (he’s the “B”), and including Tony Evnin of Venrock and Pitch Johnson of Asset Management; IDEC integrated an existing company, Biotherapy Systems, that Miller and Levy had founded in Mountain View.   In 1997, IDEC delivered rituximab, the first monoclonal antibody approved by the FDA for cancer treatment; it is also used for the treatment of rheumatoid arthritis.  IDEC merged with Biogen in 2003.

Miller ultimately left IDEC, and in 1991 teamed up with chemist Jonathan Sessler to co-found Pharmacyclics, a collaboration that reportedly began when Miller was treating Sessler for cancer at Stanford in the early 1980’s.  The company was initially focused on a class of molecules called “texaphyrins,” synthesized by Sessler (who had moved on to the University of Texas); the name may reflect either the UT origins or the resemblance of the structure to the five-point star of Texas.

While initially promising, the lead molecule,  motexafin gadolinium (Xcytrin), was unfortunately not panning out in clinical studies of brain metastases (eventually leading to a much-publicized dispute between Miller and the FDA), prompting Pharmacyclics to start thinking about a Plan B.  Enter Celera.

A Prepared Mind

The opportunity to pick up potentially promising assets from Celera – essentially, acquire an early-stage pipeline – was appealing to Pharmacyclics; while the deal apparently was initially focused only on the Phase 1 HDAC asset, Miller reportedly was keen for the BTK inhibitor program to be included as well; it was an easy request to grant, as its perceived value at the time was just about zero.

Additional studies of autoimmune disease seemed to confirm the potential of the “tool” BTK inhibitor, now designated PCI-32765; however, Miller was eager to explore its potential in B-cell cancers.  The problem was that it was hard to find appropriate models to use, either cell lines or animal models, as it was felt essential to find a model in which growth was explicitly dependent upon B-cell receptor activation, rather than bypassing it as was more commonly the case in model systems.  Ultimately, the team decided their only option was to study the drug in spontaneously occurring lymphomas in dogs, and obtained results that were suggestive, but not overwhelming.  A partial response was observed in several animals, stable disease was seen in several others.

The team struggled with what to do next.  For starters, they had reached the limits of what they felt they could learn from preclinical studies, and needed to decide, in the words of a researcher, “whether it was worth $1M” to figure out whether the promising but shaky preclinical results would translate into patients.

In addition, the team was also agonizing about whether to move forward with a molecule that worked by forming an irreversible, covalent bond; perhaps it would make more sense to go back to the chemistry lab, and try to identify a BTK inhibitor that worked by a more traditional, non-covalent mechanism.

“I Have Patients Who Are Dying”

Reportedly, Miller asked the team what were the risks of moving ahead with the covalent mechanism, and when he received vague responses, he reportedly told his colleagues, “I have patients in clinic who are dying, and need something right away.  I can’t tell them they’ll need to wait around for another year because we have a concern we can’t even articulate.”

Hence, the clinical study was initiated, and while at first it was slow to recruit, it ultimately was completed and viewed as strikingly successful.  The drug – now in phase 3, and called ibrutinib — is not a magic bullet, but may emerge as a promising option for some patients with some B-cell cancers.

On The Road Again

In another strange twist, Miller hasn’t been around to see this; he was dismissed in 2008 by the chairman of the board, Robert Duggan, who is perhaps best known as Scientology’s biggest donor.  While a Bloomberg report seems to suggest Miller’s departure reflected Duggan’s disappointment in the Xcytrin program, and his preference for focusing on B-cell cancers, I’ve also heard a very different account, suggesting it was Duggan who was keen to pursue Xcytrin, and Miller who refused, preferring instead to focus on the promising BTK inhibition program.

Miller promptly teamed up with UCSF chemist Jack Taunton to co-found Principia Biopharma, a company that focuses on “reversible covalent” molecules – drugs that form covalent bonds that release when the target protein denatures; VC backers include New Leaf, OrbiMed, Morgenthaler, SR One, and the UCSF early stage fund Mission Bay Capital.

In 2010, Miller signed on with the University of Texas as “Chief Commercialization Officer.”  However, according to reports, this role ended abruptly with his resignation less than two years later “after UT officials insisted that Miller divest his ownership interest in three startup companies that intended to license tech discoveries from the school.”   He is said to be working on a new company focused on a novel drug delivery technology.

Lessons Learned?

1.Limitations of experimental models.   In this case, the team had the insight, and the confidence, to recognize that available model systems for the study of B-cell cancers wouldn’t accurately enable assessment of their B-cell receptor-dependent mechanism, and rather than force the molecules through traditional assays (and get a false negative result), they tried to use a less traditional approach (e.g. spontaneous lymphoma model in dog), and then proceed rapidly to the clinic.

2.            Value of a translational champion: This is evident on both the academic side (e.g. inquisitive physicians such as Sharman) and on the industry side (e.g. Miller’s ability to see the clinical potential of research compound developed for different indications).

3.            Courage to value clinical need over conventional wisdom, and empiricism over theory.   Miller challenged traditional pharmaceutical reticence about covalent mechanisms in order to speed an important new drug to patients.

4.            It helps to be lucky.  For each of the lessons here – and particularly, for each of the “brave” and “bold” choices — I can easily envision how following this exact approach might have led to a far less favorable outcome, and a very different narrative (e.g. “cavalier physician imperils patients in reckless pursuit of flawed vision”).

Bottom Line: Discovering impactful new drugs is far more difficult – and far less linear – than is typically recognized.  It’s wonderful to celebrate success; our challenge is finding a way to repeat it.

9-month milestone on Ibrutinib

My son is running the Rock ‘n’ Roll San Diego Marathon to raise money for research for the Leukemia & Lymphoma Society on June 2, 2013. This event funds clinical trials for leukemia and lymphoma. Please read his story.

http://pages.teamintraining.org/az/rnr13/rharrisiij

I am personally grateful every day that I have had an opportunity to participate in a clinical trial, and I am grateful every day for the wonderful people who have funded all the clinical trials through their donations.

On another note, I just returned from the National Institutes of Health in Bethesda, Maryland last night about midnight. It was my 9-month milestone on Ibrutinib. I got the best blood work report I have had in a long while. My white blood count has gone down from 53,000 to about 35,000 in the last three months. (approximately 4,000 to 10,000 is normal). I am where I was shortly after I was diagnosed. Nothing would make me happier than to become “normalized.” Dr. Farooqui said for me NOT to expect that I will be within the normal range at my next appointment at the end of June. But as long as I am headed in the right direction, I am okay with that.

I am not anemic. My kidney function, LDH, and other organs appear normal. Hemoglobin and platelets are stable. Absolute lymphocytes are coming down. Nutriphils are normal now (They were not last time). Bone marrow does not show anything suspicious.

I am off Acyclovir, since I have not had infections. Hurrah!

My only issue is on-and-off cramping when I get in an odd position. My thumbs, my middle toes, my ankles, my shoulder blades… Strange places to be cramping. My electrolytes are not low and I am apparently drinking enough water. It happens at the oddest times. It only lasts a short while until I pull my muscle the opposite direction. Other participants have had the same side effect.

NIH doctors are keeping an eye on the unusual trisomy 13 that has cropped up in my genetics, since it has nothing to do with CLL/SLL, and may or may not develop into another blood disorder. It is not related to the trisomy 13 (Patau syndrome) in which some babies are born, involving physical and mental disorders. Trisomy 13 in adults usually doesn’t occur until people are in their 80s or 90s. I have always been told I am an “old soul,” so now I have proof. LOL.

Another strange thing is the presence of the protein CD34 on my baby platelets. Usually those are found on baby white blood cells. Doctors are researching this odd phenomena. There I go again… being an anomaly.

I am happy with the medical report. I am happy with my son and our dear friend Tyler running a marathon. And now I am off selecting the new tile for my house …

This is a new day! With smart T-Cell vaccines

Recently I had the incredible experience of having a face-to-face discussion with Dr. Lou DeGennaro, the Chief Mission Officer of the Leukemia & Lymphoma Society (LLS) in the United States, on the up-and-coming potential cure for those with 17p deleted CLL/SLL -- CARs (chimeric antigen receptors). My son Rocky made it all happen for me and I am so grateful.

On behalf of the Arizona Chapter of the LLS, Dr. DeGennaro was scheduled to give a presentation at the Ritz-Carlton in Phoenix on the topic “Someday is Today: A discussion on the latest advancements and strategies in cancer research.” Rocky invited me to the event and took me to a cocktail reception before the presentation. So with my glass of red wine in hand, Jim Brewer, the Executive Director of the Phoenix LLS, introduced me to “Dr. Lou”.

We were having such an animated and scientific discussion about CARs that I think we were boring some of the people in our circle. LOL. I have discussed CARs in prior posts, but it doesn’t hurt to summarize what this means to my potential cure.

LLS is funding Carl H. June, M.D. at the University of Pennsylvania in Philadelphia for the personalized cancer therapy he initiated on T-cell re-engineering. Dr. Weirda at M.D. Anderson is also researching CARs. In fact, there are about seven CARs trials taking place today at a variety of locations. Here is the summary of the first procedure at UPenn:

(1) T-cells are removed from the patient’s body through a procedure called “apheresis.” Blood is removed from the patient and cells are separated through a process of centrifugal force. (NOTE: I had this done when I donated my cells to science. My cells were injected in a number of mice in the NIH lab to research why I am so resilient. LOL.) This is a painless procedure, similar to donating blood to a bank. My friend Janis witnessed me resting in the bed during this procedure in June of last year.

(2) The extracted T-cells from the patient are engineered to express a “chimeric antigen receptor” (CARs). The T-cells are harvested and injected with benign HIV cells.

(3) After the T-cells are re-engineered, they are ready to be infused back into the patient.

(4) The T-cell “serial killers” erradicate the cells with the CD19 enzyme, and the procedure climaxes at about two weeks or so. Because healthy B-cells also have CD19, the engineered T-cells cannot differentiate and kill them as well.

(5) The patient often has the worst case of the “flu” ever with sometimes a fever of 104 degrees.

NOTE: The first three clinical trial subjects at UPenn were rushed to the hospital thinking they were dying. Shortly after the episode, the three patients were tested for cancer, and found that there was no leukemia in two and a minimal residual disease (a small number of leukemia cells remaining, but no symptoms or signs of disease) in one.

NOTE: I was unable to credit the graphic designer who did this informational graphic, because there was no name attached to the image. If you are out there, let me know and I will give you full credit for your work.

For those of you not wanting the timeline details, skip to the paragraph after the indented text.

CARs TIMELINE

• In 1987 it was discovered that CD28 is the gatekeeper for T-cell proliferation.

• CARs research was actually pioneered in vitro in 1989, but it took two decades for it to be tried on humans.

• In 1993 a CD culture system was produced with CD3/CD28 beads. Cell size were 4.5 microns each and they were grown in vitro (test tubes)

• Three clinical trials were conducted in 1998 with HIV patients.

The first HIV CAR patients were treated targeting CD4z modified T-cells. They were infused with the re-engineered T-cells like a blood transfusion. 41 of 43 patients have CAR T-cells that have persisted more than a decade with no adverse effects.

• In 2006 the first cancer patients were treated NCI and in the Netherlands. No clinical efficacy, because T-cells did not engraft on the patients. Cells had half-lives and lasted less than a week.

• Clinical trial.gov #NCT01029366 at the University of Pennsylvania treated 12 subjects as of September 2012:

July 31, 2010 the first cancer subject was treated. The target was CD19, since it is expressed on the surface of most B-cell malignancies. Ten patients had CLL/SLL and two had ALL (acute lymphocytic leukemia). The patients were infused a 10-30-60% dose for three days. Seven had a complete remission (CR). Two had a partial remission (PR), and three had no remission (NR). No one has relapsed, and T-cells continue to produce antibodies (Now for two years). Each person had a total of 3.5 to 7 pounds of tumor cells removed from their body through this procedure. Each re-engineered CAR T-cell (“serial killers”) can kill 1,000 tumor cells.

My Australian blog friend John also passed on these links for my nerdy friends wanting more information on CARs:

• Interview with William Wierda on CARS at

http://www.patientpower.info/video/new-t-cell-car-research-for-cll?autoplay=1


• CLL Global Research magazine 2-2012, particularly Page 4 for Kinase inhibitors & CARS at http://www.cllglobal.org/Resource_Files/CLL_NL_Issue2_2012.pdf 


• CARS research, a talk by Dr. carl June at

http://www.youtube.com/watch?v=jQfFCC6i5_o.

The initial problems with the CARs trial at UPenn were:

(1) the enzyme CD19 is also found on normal B-cells, so patients are left immune compromised,

(2) Because the T-cells are harvested from each patient, it is an expensive and time-consuming procedure, and

(3) the patient has to be in good enough health to provide enough T-cells.

Researchers are getting closer to a cure. Future solutions:

(1) Now the new procedure involves re-engineering T-cells to bind with a certain protein – ROR1, which is expressed in leukemia cells. ROR1 becomes the target.

(2) In order to be more cost-effective, as well as efficient, researchers are exploring using healthy donor cells. This will also help those patients who are deficient in T-cells to harvest.

An interesting bit of information is that research and finding treatments and cures for blood cancers often leads to application to other cancers. For example, the CARs trial at the University of Pennsyvania is now using the concept of the re-engineered T-cells for trials in pancreatic cancer. This CARs immunotherapy is a cure for leukemia and it is just around the corner. This is a new day!

Check out this video:

http://vimeo.com/54668275

CLINICAL TRIALS

Over one million people in North America alone were affected with blood cancer this year, according to the Leukemia & Lymphoma Society. Anyone can get blood cancer. Scientists are studying the possible familial connection or environmental connection. Sometimes it is just plain luck of the draw.

Last month I attended an informative Leukemia & Lymphoma Society event at Arizona State University’s Sky Song in Scottsdale on the topic of clinical trials. I now wish to take this gift of knowledge and pass it on to all the readers of my blog.

CLINICAL TRIALS

If you qualify for a cancer clinical trial, my first response would be: “What are you waiting for?” The majority of participants find that a clinical trial is a positive experience, and that they were treated with quality medical care, dignity, and respect (Harris Interactive 2001). I will second that motion. Having a research doctor answer the questions you have submitted by email with a personal phone call is the best kind of medicine. I know how busy they are, so I try not to abuse this wonderful option.

On the practical side, it does cost money, if the clinical trial is far from your home. We have spent a good amount of money this past year on flights, hotels, and meal stipends to travel across the United States from Arizona. NIH reimbursed about one-third of the costs, which helped a lot. Some sites do not reimburse any travel costs. Many participants are lucky to find a clinical trial near their home and they can drive or have someone drive them. Since traveling is stressful, you also need to consider whether the patient is physically able to travel and be away from home.

Every available cancer therapy begins with research. Researchers are not able to begin their discovery without funding. That is why research grants are so vital. So here is a shout out to all those people who raise funds for research! Thank you.

Once funding is available, the development of the therapy is accelerated through clinical trials. The trial, however, is at a standstill until cancer patients volunteer to participate. The sooner the number of participants is reached, the sooner the research is conducted and presented.

 Clinical trials go through several phases. In a nutshell, here is a summary of the phases:

• Phase I trials test for safety of the drug, the best way to administer it, and if cancer responds.

• Phase II trials test if one particular type of cancer responds to the new treatment. Everyone gets the drug. For example, I am in a Phase II clinical trial and the arm of the trial I am in is for participants over the age of 18, who are untreated or treated, who have the poor prognosis of 17p deletion.

• Phase III trials compare the new treatment to the standard treatment, and test to see if it works better. There is no placebo. The computer determines whether you get the new drug or the standard treatment.

• Phase IV trials continue researching long-term benefits and side effects.

The process costs time and money, and requires investigators, institutions, the federal government, the pharmaceutical industry, and the public to cooperate and trust the process. Here is an interesting fact from Banner M.D. Anderson (MDA): Out of 5,000 great ideas, five go to clinical trial, but usually only one gets approved by the United States Food & Drug Administration (FDA). The average cost is over one billion dollars for a new drug application (NDA). The NDA is the process through which drug sponsors propose that the FDA approve of a drug for sale to be marketed in the U.S and become commercialized and available to patients.

Without clinical trials there would be no new cancer therapies. Funding and participants are integral to the success of cancer research.