title: Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.
abstract: We undertook a Phase I/II trial in patients with apparent recurrent glioblastoma multiforme (GBM) based on imaging studies to determine the safety and tumor response of repetitive intravenous administration of NDV-HUJ, the oncolytic HUJ strain of Newcastle disease virus. The first part of the study utilized an accelerated intrapatient dose-escalation protocol with one-cycle dosage steps of 0.1, 0.32, 0.93, 5.9, and 11 billion infectious units (BIU) of NDV-HUJ (1 BIU = 1 x 10(9) EID(50) 50% egg infectious dose) followed by three cycles of 55 BIU. Virus was administered by intravenous infusion over 15 min. In the second part, patients received three cycles of 11 BIU. All patients without progressive disease were maintained with two doses of 11 BIU iv weekly. Eleven of the 14 enrolled patients (11-58 years, Karnofsky performance scale 50-90%) received treatment. Toxicity was minimal with Grade I/II constitutional fever being seen in 5 patients. Maximum tolerated dose was not achieved. Anti-NDV hemagglutinin antibodies appeared within 5-29 days. NDV-HUJ was recovered from blood, saliva, and urine samples and one tumor biopsy. One patient achieved a complete response. Intravenous NDV-HUJ is well tolerated. The findings of good tolerability and encouraging responses warrant the continued evaluation of NDV-HUJ in GBM, as well as other cancers.
authors.affiliation: Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem 91120, Israel.
authors.forename: Arnold I
authors.initials: AI
authors.lastname: Freeman
authors.forename: Zichria
authors.initials: Z
authors.lastname: Zakay-Rones
authors.forename: John M
authors.initials: JM
authors.lastname: Gomori
authors.forename: Eduard
authors.initials: E
authors.lastname: Linetsky
authors.forename: Linda
authors.initials: L
authors.lastname: Rasooly
authors.forename: Evgeniya
authors.initials: E
authors.lastname: Greenbaum
authors.forename: Shira
authors.initials: S
authors.lastname: Rozenman-Yair
authors.forename: Amos
authors.initials: A
authors.lastname: Panet
authors.forename: Eugene
authors.initials: E
authors.lastname: Libson
authors.forename: Charles S
authors.initials: CS
authors.lastname: Irving
authors.forename: Eithan
authors.initials: E
authors.lastname: Galun
authors.forename: Tali
authors.initials: T
authors.lastname: Siegal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009522:Newcastle disease virus; D050130:Oncolytic Virotherapy / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents