The time to re-establish safe levels of neutrophils and plateletsin patients with lymphoma who have undergone bone marrowtransplant is shorter when the cytokines interleukin-3 (IL-3)and granulocyte macrophage-colony stimulating factor (GM-CSF) are administered sequentially than for GM-CSF alone.
This conclusion was drawn from an ongoing analysis of thePhase II clinical trial data generated by the CytokineDevelopment Unit (CDU) of Sandoz Pharmaceuticals Corp.
Speaking at Cowen & Co.'s Eighth Annual Healthcare Conferencein San Francisco this week, CDU's executive director, DanielLevitt, explained that the Phase II data on 52 patientsreconfirm what the company had found when it analyzed thefirst 15 patients, and then the first 32: that the combination ofIL-3 and GM-CSF is synergistic.
According to Levitt, historical data has shown that without anycytokine therapy, such patients require about 28 days to re-establish their platelet and neutrophil counts to safe levels. Ifdosed with GM-CSF, the time is reduced to about 19 days torestore the neutrophils, but it still takes about four weeks tobring up the platelet count. However, when sequential cytokinetherapy is employed, this time drops to about 15 days, Levitttold BioWorld.
He claimed that the data are also better than for thesimultaneous administration of IL-3 and GM-CSF (ImmunexCorp.'s product PIXY321, which is a fusion protein containingboth cytokines).
"The data on PIXY321 (reported by Immunex in May at theAmerican Society of Clinical Oncology meeting) indicate that ittakes 19 to 20 days to restore both the neutrophils andplatelets," Levitt said.
Sandoz's CDU, located in East Hanover, N.J., began enrollingpatients in the Phase III trial on sequential administration ofIL-3 and GM-CSF in late June; it intends to enroll about 150patients with Hodgkin's disease or non-Hodgkin's lymphomawho are also undergoing bone marrow transplant.
CDU researchers are also investigating the clinical attributes ofthe cytokine interleukin-6 (IL-6). Levitt reported Phase Isafety data of IL-6 at the Cowen meeting and several daysearlier at a Serono Symposium on "Platelets and CellularSupport in Clinical Oncology" held in Arlington, Va.
"We've treated over 300 patients with the drug in the U.S. andanother 230 in Europe," he said. "At doses that appear tostimulate platelet counts, IL-6 is safe." Those doses can rangeanywhere from 0.5 micrograms per kilogram body weight perday to 50 micrograms.
CDU is currently conducting Phase IIs in both Europe and theU.S., testing the ability of IL-6 in combination with either GM-CSF or G-CSF (granulocyte-colony stimulating factor) to rapidlyrestore platelet counts after different forms of chemotherapy,and after bone marrow or stem cell transplant in patients withbreast cancer, Levitt told BioWorld. He added that CDUanticipates starting Phase III trials in the first quarter of 1994.
With the exception of G-CSF, which Sandoz buys from AmgenInc. (NASDAQ:AMGN), the cytokines that CDU is using in itstrials were originally identified and cloned by scientists fromGenetics Institute Inc. (NASDAQ:GENIZ). Sandoz holds theworldwide marketing rights from GI for IL-3 and IL-6 and isalso GI's licensee for GM-CSF, which it sublicensed to Schering-Plough Corp.
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.