Pharmacyclics: Xcytrin/Zevalin combo shows anti-tumor activity in lymphoma patients

By Angela McDaniels

Seattle, Dec. 12 - Pharmacyclics Inc. said preliminary results of a phase 1 clinical trial suggest that Xcytrin (motexafin gadolinium) injection, when given in combination with Zevalin (Ibritumomab Tiuxetan), is well tolerated and demonstrates synergistic activity in patients with Rituxan-refractory, low-grade and transformed non-Hodgkin's lymphoma.

The ongoing, dose-escalation phase 1 study included patients who had failed an average of three prior treatment regimens. Four doses of Xcytrin were administered each week for two weeks with one injection of 90 Yttrium Zevalin.

Six complete and one partial tumor responses were seen out of nine patients. Of the patients with follicular histology, five have achieved a complete response, and one has achieved a partial response. One of the patients with transformed diffuse B-cell histology has achieved a complete response. No response was observed in the one patient with mantle cell histology.

Only one of the responding patients has relapsed, after eight months; all others are still in remission ranging from two to 13 months, the company said.

No dose-limiting toxicity has been seen to date.

"We found that Xcytrin, when combined with Zevalin, does not appear to increase hematologic or other toxicity," said lead investigator Andrew M. Evens of Northwestern University in a company news release.

"Moreover, we observed prompt tumor responses and complete remission in a high proportion of refractory lymphoma patients. The goal of the study is to utilize the potential single agent activity of Xcytrin with its radiation enhancing properties."

The data was presented at the American Society of Hematology 47th annual meeting being held this week in Atlanta.

A second phase 2 study reported that Xcytrin demonstrated single-agent activity in refractory low-grade lymphoma and chronic lymphocytic leukemia.

Ten patients with low-grade lymphoma received Xcytrin daily for three days every two weeks and two patients with chronic lymphocytic leukemia received the drug every day for ten days every three weeks. Enrolled patients had failed a median of 3.5 prior treatment regimens.

There have been three partial responses and two patients had stable disease, one with resolution of autoimmune hemolytic anemia, the company said.

Responses occurred after two or fewer cycles of therapy with Xcytrin and were seen in patients failing extensive prior treatment (median of 4.3 prior regimens).

Xcytrin-related adverse events included blisters around fingernails, skin and urine discoloration, diarrhea, nausea and peripheral neuropathy, the company said.

Chronic lymphocytic leukemia is a malignancies of bone marrow and blood. Tumor cell growth in these patients usually causes an elevation of peripheral blood white cell counts and infiltration of bone marrow, lymph nodes, spleen and other organs.

Non-Hodgkin's lymphomas are often widely disseminated through multiple lymph node sites, the bone marrow and other organs. Although they often respond to initial chemotherapy, most patients with relapsed B-cell non-Hodgkin's lymphomas are not cured with existing treatments. Zevalin is an approved radiolabeled monoclonal antibody used in the treatment of this disease, but complete responses are seen in less than 30% of patients, the company said.

Pharmacyclics is developing Xcytrin as an anti-cancer agent designed to selectively concentrate in tumors and induce programmed cell death. Its multifunctional mode of action provides the opportunity to be used in a broad range of cancers, the company said.

Pharmacyclics said it has been granted fast track status by the U.S. Food and Drug Administration for Xcytrin for the treatment of brain metastases in patients with non-small cell lung cancer.

Pharmacyclics is a pharmaceutical company based in Sunnyvale, Calif. that develops products

to treat cancer, atherosclerosis and other diseases. The company's products are designed to selectively target and disrupt the bioenergetic processes of diseased cells, such as cancer and atherosclerotic plaque.

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