Blood Cancer &
 Leukemia

Funds awarded for research into Fallon leukemia cluster

June 18, 2004
A top Arkansas cancer researcher was awarded $224,000 from the Environmental Protection Agency Thursday to study genetic links in children included in the Fallon leukemia cluster.

Dr. Jill James, director of the study and a biologist at the Arkansas Children's Hospital Research Institute, told the Lahontan Valley News in April that her study will expand on the federal and state leukemia cluster investigation, which concluded earlier this year. The University of Nevada, Reno will provide administrative support for her research.

In the Fallon leukemia cluster 16 children have been diagnosed since 1997 and three have died. It's been about two years since the last case was added to the cluster.

She is interested in studying how a child's genetic makeup might increase his or her vulnerability to DNA damage from the metals found in Fallon's drinking water, and whether this could increase the child's risk of leukemia. Those metals include arsenic, antimony, tungsten and cobalt.

Sen. Harry Reid, D-Nev., said James was chosen because of her reputation with researching arsenic. The money for this study was granted in the 2003 Omnibus Appropriations Bill.

The Center for Disease Control and Prevention's leukemia cluster investigation found 80 percent of the leukemia case families and control subjects tested had elevated levels of tungsten in urine samples, while only one person in 10 does nationally. High levels of several other metals were also found.

The investigation's expert panel, which released its final report in February, said the results did not explain the cause of the leukemia cluster, but it also said this cluster was not a chance occurrence.

James said she hopes to interview and take blood samples from all 13 of the case children and their mothers. She will have two control groups, one from Fallon and another from Arkansas. The Arkansas control group is important, she said, because they will have no exposure to any of the metals in the Fallon environment.

Even though the CDC concluded that no single metal exposure could explain an increased risk of cancer, James is considering that the combined exposure to several of the metals that are known to damage DNA could be additive and sufficient to trigger the disease.

Fallon resident Jeff Braccini, whose son was diagnosed with acute lymphocytic leukemia in December 2001, said he is glad to hear this news but there is still a lot more to do.

"We knew it was coming and we're glad it finally came through," he said. "This is a very good thing. It continues research but there still is a lot more to do."

He said Families in Search of Truth, a non-profit organization devoted to finding the truth behind the cause of the Fallon leukemia cluster, complied a list of independent researchers to do work on the cluster and James' name was on that list.

US FDA Accepts Genmab's IND for HuMax-CD20 to Treat CLL

Monday June 21, 3:19 am ET
COPENHAGEN, Denmark, June 21 /PRNewswire-FirstCall/ -- Genmab A/S (CSE: GEN - News) announced today the US Food & Drug Administration (FDA) has accepted its Investigational New Drug (IND) application to start an open-label dose escalation Phase I/II study with HuMax-CD20 to treat patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL).

A total of 32 patients will be treated for four weeks and will initially receive either a 100 mg, 300 mg or 500 mg dose of HuMax-CD20, followed by three weekly doses of 500 mg, 1000 mg or 2000 mg, respectively. The highest dose group treated will be expanded to include a total of 26 patients in order to obtain more information about efficacy. The total follow up period is 12 months from treatment start and the primary endpoint of the trial is objective response over the period from screening to week 19. Genmab will initiate the study during the summer of 2004.

About HuMax-CD20

HuMax-CD20 is a human antibody which is effective at binding to the disease target, and releases only very slowly from the target over time. In February 2003, Genmab presented data from pre-clinical laboratory tests showing HuMax-CD20 appeared to kill tumor cells from cancer patients who had CLL that were resistant to rituximab, a marketed cancer therapy. The data showed the antibody highly effective in inducing complement mediated cytotoxicity (cell destruction) of B- cell tumors. Subsequently, Genmab has collected data that appears to show HuMax-CD20 is also effective in inducing Natural Killer cell-mediated cytotoxicity of B-cell tumors. Further, in a 92 day primate study, HuMax-CD20 effectively depleted B-cells from blood and lymph nodes. In this study, HuMax-CD20 appeared to deplete B-cells for a period of time that was four times longer than rituximab.

In another study it was found that HuMax-CD20 binds to a unique site on CD20 target cells when compared to other known CD20 antibodies. This is a distinguishing characteristic of HuMax-CD20 and may help explain why HuMax- CD20 has outperformed other CD20 antibodies in a variety of pre-clinical studies. Furthermore, in a novel cancer disease model in immuno-compromised mice using sensitive bio-luminescence imaging, new data show that HuMax-CD20 appears to stop growth of B-cell tumors grown from a laboratory cell line far more effectively than either placebo, or rituximab.

HuMax-CD20 is currently in an ongoing Phase I/II study to treat patients with relapsed or refractory follicular lymphoma.

About CD20

The CD20 antigen is a transmembrane protein on pre-B and mature B lymphocytes. CD20 appears to act as a calcium ion channel, and to regulate early steps in B lymphocyte activation. The molecule is not shed from the cell surface, and is not internalized upon antibody binding. CD20 is found on over 90% of B-cell lymphomas, as well as other lymphoid tumors of B-cell origin.

About Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia is the most common leukemia in adults in the US and most of Western Europe. The incidence is 8,100 to 12,500 new cases in the US per year and 85-95% of the cases are of B-cell origin. CLL is a subgroup of Non-Hodgkin's lymphoma (NHL) and together with small lymphocytic lymphoma (SLL) corresponds to around 20% of all NHL cases.

About Genmab A/S

Genmab A/S is a biotechnology company that creates and develops human antibodies for the treatment of life-threatening and debilitating diseases. Genmab has numerous products in development to treat cancer, infectious disease, rheumatoid arthritis and other inflammatory conditions, and intends to continue assembling a broad portfolio of new therapeutic products. At present, Genmab has multiple partnerships to gain access to disease targets and develop novel human antibodies including agreements with Roche and Amgen. A broad alliance provides Genmab with access to Medarex, Inc.'s array of proprietary technologies, including the UltiMAb(tm) platform for the rapid creation and development of human antibodies to virtually any disease target. Genmab is headquartered in Copenhagen, Denmark, and has operations in Utrecht, The Netherlands, and Princeton, New Jersey in the US. For more information about Genmab, visit http://www.genmab.com.

Leukemia survivor meets life-saving marrow donor
Army major, recipient unite at transplant center

Wednesday, June 23, 2004
The man who saved Bill Bryan's life more than a year ago lived only one state away. A mere six-hour drive. But until Tuesday morning, Bryan never had given him a proper thank you - and he had never seen his face.

Bryan, 60, fell victim to leukemia in 2001, but an anonymous donor gave him bone marrow for a transplant in 2003 that sent him on the path to recovery. Amid applause, hugs and a few tears in the UAB bone marrow transplant center Tuesday, Bryan's benefactor, Army Maj. Stan Borden III, was finally there to receive thanks.

"I owe my life to him," Bryan said to the crowd of nurses and doctors who witnessed the meeting. "What else could I say?" The one-year delay in meeting was not on purpose. Bryan and Borden were linked up through the National Marrow Donor Program, a nonprofit group that matches leukemia patients with donors who have a similar type of bone marrow. After the transplant, donors and recipients are not allowed to have a personal relationship until the transplant is deemed a success - usually one year after the operation.

Borden, 42, now one of the head nurses at Fort Stewart, Ga., was always eager to be a donor. Inspired by a leukemia survivor he met at the Army War College in Pennsylvania, he placed himself on the donor list in the mid-'90s. But after being matched with a recipient, Borden came across an unexpected hurdle. "Just before I had gotten the call, I was notified I was going to Iraq."

The next few weeks were a series of ups and downs for Bryan, who lives in Montgomery. "I knew that my chances weren't good, even with a perfect donor," he recalled. "When they said I didn't have a donor, they were just going to send me home." At the last minute, though, Borden was taken off the Iraq list. Bryan said he was elated when he found out his donor was back on line, but he remained aware of the risks.

"The chances are so slim of success," he said. "The day I showed up there were three of us getting transplants. Two of them didn't make it." Bryan expressed his gratitude Tuesday for Borden's recall from going to Iraq. "I know you're disappointed you didn't get to go," he said with a smile, "but I'm glad you're here." UAB doctors and nurses who were involved in the transplant process said the meeting meant as much to them as it did to the donor and recipient.

"It's not every day you get to see someone actually meet their donor," said Diana Tate, the bone marrow transplant coordinator at UAB Hospital. Tate herself was a transplant success story before she started working in the unit. As the nurses and doctors filed back to work, Borden presented Bryan with a limited edition Army anniversary coin as a memento.

"It's just something to kind of remember me by," Borden said.

Bryan looked up and smiled in return.

"Well, I don't think I'll have any trouble doing that."

Despite setbacks, Genta tries to prove it's one biotech company that can rebound

SUSAN TODD

Associated Press

Jun. 27, 2004
BERKELEY HEIGHTS, N.J. - When Genta failed to get approval for its cancer drug last month, Raymond Warrell, chief executive of the battered biotechnology company, began a ritual of lunchtime meetings with his employees.

No question or rumor was off limits.

Warrell, a former oncologist with a calm, serious manner, took them all. He explained everything from the data scrutinized by the Food and Drug Administration's panel of experts to a flurry of lawsuits filed by angry shareholders.

At the fourth meeting, he tried a new tactic: optimism.

Using slides projected on a big screen, he presented stock charts for six biotech companies that ran into snags in developing drugs. In each case, share prices slid and then rebounded as the business recovered.

It was proof, Warrell said, that biotech companies do rebound.

"This is a very dynamic, highly volatile business," Warrell said in an interview this week. "As rapidly as things can collapse, things can snap back."

Now, he is hoping to prove it with Genta, once one of New Jersey's most promising biotechnology companies. But by all accounts, it won't be easy.

For starters, the company must prove its key drug, Genasense, treats chronic lymphocytic leukemia. And Genta has to be more convincing than it was last month when an FDA panel recommended against approving Genasense as a treatment for skin cancer.

(Companies that make cancer medicines often seek approval of the same drug for different forms of the disease.)

Warrell, meanwhile, has a variety of other challenges, including limited cash, shareholder lawsuits and skeptical investors.

"If the data on (leukemia) is bad, you have to doubt the future of the company," said David Miller, president of Biotech Monthly, an independent stock research publication in Seattle. "It's all about the data.

"I don't think their credibility can get any worse than it is. What they have is a financial risk. They have to worry about keeping the lights on."

In his first interview since Genta's stumble last month, Warrell, 54, described the company's sudden, wrenching shift into recovery mode.

It began on May 3. Nearly every Genta employee was either attending the FDA advisory panel meeting in Maryland or watching it via teleconference at the company's offices in Berkeley Heights.

The panel said Genta's studies did not sufficiently prove Genasense, combined with the chemotherapy drug dacarbazine, helped patients with malignant melanoma.

FDA observers said the agency's reviewers were unusually scathing. The vote represented a departure, they said, from the agency's recent leniency on new cancer medicines, such as AstraZeneca's Iressa for lung cancer.

"We were optimistic this application had a good shot at approval," Warrell said. "We're certainly hopeful that other indications or the melanoma indication will prove to be successful. It wasn't on that morning."

The disappointment was immense. Genta has spent nine years and $323 million developing Genasense. And it has cost Genta dearly.

The company's stock price has plummeted 77 percent since the start of the year, and 85 employees were fired, including a newly assembled 35-member sales force. With its sales force eliminated, Genta's management also stopped marketing its only product, Ganite, a treatment for elevated levels of calcium in cancer patients.

Those steps will help Genta's financial situation. In the last quarter, Genta had at least $67 million - enough to take the company into next year.

"The worst time was probably the first 48 hours (after the advisory panel's meeting)," Warrell said, "realizing the full implication of this decision with respect to the company our team had built."

The company's fate still rests with Genasense. The drug is being studied in late-stage clinical trials as a treatment for two forms of blood cancer, leukemia and multiple myeloma.

Aventis, Genta's partner in developing Genasense, is standing behind its $477 million agreement. However, when the company's merger with Sanofi-Synthelabo is completed, analysts expect the terms of the 2-year-old pact could change.

Even if the two late-stage clinical studies produce positive data later this year, the company must still return to the FDA for approval.

Genta is hoping to seek its next approval by the end of 2004.

"You hope they're not going to happen, but every company has its bumps," said Douglas Watson, a director on the company's board since 2002. "We're very much believers in Genasense. We're hopeful these other indications will breathe life into it."

Analysts said Genta's best bet at resurrection rests with the drug's ability to treat chronic lymphocytic leukemia. "Genasense works," Miller said. "It's a matter of determining which markets it works in."

It is also a matter of money. The tough decisions Warrell and his senior management made within days of the panel's vote will give it more cash to use as it pursues regulatory approval for Genasense.

If it succeeds in getting an approval, Genta could receive an additional $95 million from Aventis. An approval will be a "springboard," Warrell said, "to bring other products into the company."

During the company's annual meeting Wednesday, Warrell put aside concern over whether his credibility is an issue as the company moves ahead.

"The issue is really how well this drug performs, management's ability to maneuver through the regulatory process and to manage our resources," he said.

"We have been clear from the outset about the risks of investing in projects for difficult diseases."

Genta deliberately diversified its program, he said, so if Genasense failed in one area, there would be multiple chances of getting approval in another. Now, the company is relying on its fallback strategy.

"With luck," Warrell said, "the other two clinical trials will be part of the turnaround process."

New Drug Treatments Offer Hope to Leukemia Patients

By Dennis Thompson
HealthDay Reporter

TUESDAY, Sept. 28 (HealthDayNews) -- Scientists call them "molecularly targeted" drugs, and they represent a remarkable gain in the war against blood cancers.

Leukemia, lymphoma and myeloma are some of the rarest yet most deadly forms of cancer. They account for only 2 percent to 3 percent of all cancers, but cause 10 percent of all cancer deaths, said Alan Kinniburgh, vice president of research for the Leukemia & Lymphoma Society.

These so-called "liquid cancers" cannot be surgically removed and up until recently have been treated with radiation and chemotherapy.

But promising new therapies all involve "molecularly targeted" drugs that disrupt the spread of cancer by honing in on specific mechanical processes that cancer cells to grow.

These breakthrough treatments merit attention in September, which is Leukemia & Lymphoma Awareness Month.

Kinniburgh foresees a day when these new drugs will work together to halt blood cancers, "all hitting the same target, but hitting the target in different ways so the target can't escape being killed."

An estimated 106,000 Americans were diagnosed with leukemia, lymphoma or myeloma last year, according to estimates by the National Cancer Institute (news - web sites). Another 57,500 people died from one of the diseases.

The diseases each begin with one damaged cell that turns cancerous, explained Hildy Dillon, vice president of patient services for the Leukemia & Lymphoma Society.

"They are usually the result of an acquired genetic injury to the DNA of a single cell, which then becomes malignant and starts to reproduce," Dillon said.

The blood cancers interfere with the production of healthy blood cells, Dillon said.

If red blood cells are affected, the person initially suffers from anemia and fatigue. If white blood cells are stricken, the patient initially suffers a high risk of infection. And since the cancers affect blood's ability to clot, patients also suffer unexplained bruises.

If left untreated -- or detected too late -- the blood cancers will kill.

The biggest recent leukemia breakthrough involved the drug Gleevec, which inhibits an enzyme that pushes cells to reproduce uncontrollably. The drug, which gained U.S. Food and Drug Administration (news - web sites) approval in 2001, has been stunningly successful in treating people with chronic myeloid leukemia, often returning patients' blood cell counts to near normal within three or four weeks.

Building on the success of Gleevec are three other new therapies that hold promise, Kinniburgh said.

The first involves clofarabine, a drug that disrupts DNA replication in cancer cells. The drug has been found in clinical trials to put about one-quarter of acute lymphoblastic leukemia (ALL) patients and acute myeloid leukemia (AML) patients into remission when other treatments have failed, Kinniburgh said.

"That provides extra time for a patient to undergo a bone marrow or stem-cell transplant," he said. "That's going to save children's lives." The drug is awaiting FDA (news - web sites) approval.

Another set of drugs undergoing clinical trials are FLT-3 inhibitors, which can disrupt cellular communications that spur cancer growth. Again, about one-quarter of patients with acute myeloid leukemia respond to the drugs, but those who do respond show an 80 percent to 90 percent reduction of cancer cells in the blood, Kinniburgh said.

The third drug, which Kinniburgh calls "Son of Gleevec," is an ABL-kinase inhibitor that targets cancer cell mutations that escape treatment with Gleevec. The drug, BMS-354825, is being tested in patients with chronic myelogenous leukemia whose bodies are resistant to Gleevec.

Doctors generally don't know what causes blood cancers. Benzene, smoking, radiation and the Epstein-Barr virus have all been linked to the diseases, but most of the time physicians have no idea why a specific person has contracted a blood cancer.

"Most often, there really isn't a known cause," Dillon said. "These are not diseases that can be prevented."

There also are multiple types of each of the diseases, which can make it tough for doctors to know how to proceed, Dillon said.

"The challenge is to determine the type of blood cancer a person has because the treatments are designed very specifically," she said. "They're beginning to be able to really target the specific mechanics of each of these different types of cancer.

Leukemia involves cancer of the bone marrow and blood cells, and strikes about 30,600 Americans each year. Another 21,900 die from the disease annually.

Lymphomas are malignancies of the lymphocites, a type of white blood cell. This is the most common blood cancer, afflicting 61,000 people a year and killing 24,700.

Myeloma affects the plasma cells, or white blood cells found primarily in the bone marrow. About 14,600 people are diagnosed with this disease each year, and another 10,900 die.

Leukemia has a five-year survival rate of 44 percent. Lymphoma has a 52 percent survival rate, and myeloma has a 28 percent survival rate.

Kinniburgh said all of the new drug treatments could ultimately be used in concert to specifically target different blood cancers, no matter how rare or obscure.

"With several of these agents hitting each other's cross-resistance, it's certainly very likely we may be able to treat all patients without radiation or chemotherapy," he said. "At some point the goal and the dream would be the drugs could be withdrawn from the patients and they would go on in remission."

More information

To learn more about blood cancers, visit the Leukemia & Lymphoma Society.

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