1. ¹Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem 91120, Israel
2. ²Department of Virology, Hebrew University, Jerusalem 91120, Israel
3. ³Department of Neuro-radiology, Hadassah University Hospital, Jerusalem 91120, Israel
4. ⁴Department of Neurology, Hadassah University Hospital, Jerusalem 91120, Israel
5. ⁵Gaffin Center for Neuro-Oncology, Hadassah University Hospital, Jerusalem 91120, Israel
6. ⁶Theravir Management LP, Jerusalem, Israel
7. ⁷Department of Radiology, Hadassah University Hospital, Jerusalem 91120, Israel

Correspondence: Eithan Galun, Fax: +972 2 642 9856. E-mail: galun@md2.huji.ac.il

Received 19 May 2005; Revised 30 August 2005; Accepted 30 August 2005.

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 = 1 10⁹ EID₅₀ 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.