The Cytokine Development Unit (CDU) of SandozPharmaceuticals Corp. announced Wednesday that it hasinitiated a Phase III clinical trial to evaluate the ability ofsequential cytokine therapy to repopulate blood cells in post-bone marrow transplant cancer patients.

Specifically, the trial will evaluate the effects on theregeneration of neutrophils and platelets of interleukin-3 (IL-3) and granulocyte macrophage-colony stimulating factor (GM-CSF) given sequentially, as compared to GM-CSF alone.

CDU intends to enroll approximately 150 patients diagnosedwith Hodgkin's disease or non-Hodgkin's lymphoma andundergoing bone marrow transplant (BMT) in the multicenter,double-blinded trial. CDU is currently screening patients forthis trial, said Alain Delongchamp, director of new productmanagement.

"Based on clinical results from a Phase II study, thecombination of IL-3 and GM-CSF has been shown to have asynergistic effect on accelerating the production of white bloodcells in lymphoma patients following BMTs," said Joseph Fay,director of BMT services at Baylor University Medical Centerand principal investigator in the Phase III trial.

The company reported Phase II data on 26 patients last fall atthe annual meeting of the American Society of Hematology,Delongchamp said. (There are now 42 patients in that study.)In that trial, patients treated with IL-3 and GM-CSF exhibitedneutrophil engraftment in an average of 15 days, compared tohistorical controls of 19 days with GM-CSF alone, while plateletengraftment occurred in 14 days, as compared to historicalcontrols of 26 days with GM-CSF alone.

The historical controls came mainly from data in the keyregistration file that John Nemunaitis published in The NewEngland Journal of Medicine on Immunex Corp.'s GM-CSF(Leukine), according to Delongchamp.

In fact, CDU, which is a functionally autonomous unit of SandozPharmaceuticals of East Hanover, N.J., is still enrolling patientsin the Phase II trial, according to Delongchamp, and "gatheringmore safety and efficacy data as we go along."

Because recent research has shown that IL-3 stimulates theearly stages of blood cell development, while GM-CSF regulateslater-stage maturation events, CDU chose to administer thecytokines sequentially rather than simultaneously (as per theapproach that Immunex Corp. has taken with its IL-3/GM-CSFfusion protein PIXY321).

"In the Phase IIs we studied a number of ways to administerthe cytokines. ... We got the greatest response when IL-3 wasadministered first for 10 days and then GM-CSF wasadministered on the 11th day," Delongchamp told BioWorld.

The cytokines that CDU is using in its trials were originallyidentified and cloned by scientists from Genetics InstituteInc.(NASDAQ:GENIZ). CDU's parent company, Sandoz, holds theexclusive worldwide marketing rights from GI for IL-3; Sandozis also GI's licensee for GM-CSF, which it sublicensed toSchering-Plough Corp.

Immunex's (NASDAQ:IMNX) cytokine combo PIXY321 (IL-3/GM-CSF) is also in clinical trials.

In fact, Phase I/II trial data will be presented in six differentpapers at next week's meeting of the American Society ofClinical Oncology in Orlando, Fla. These trials are investigatingPIXY321's use as an adjunct treatment to chemotherapy.Multicenter Phase II/III trials of PIXY321 started in November1992, according to Jason Rubin, Immunex's vice president ofcommunications. Phase IIIs are scheduled to begin this year,Rubin told BioWorld.

-- Jennifer Van Brunt Senior Editor

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