A Phase I Study of the Anti-Idiotype Vaccine Racotumomab in Neuroblastoma and Other Pediatric Refractory Malignancies

WALTER CACCIAVILLANO; CLAUDIA SAMPOR; CECILIA VENIER; MARIANO R. GABRI; MAR
A T.G. DE D
AVILA; MARIA L. GALLUZZO; MARCELO D. GUTHMANN ; LEONARDO FAINBOIM ; DANIEL F. ALONSO; GUILLERMO L. CHANTADA

PEDIATRIC BLOOD & CANCER

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2015 vol. 60 p. 2120 - 2124

1545-5009

Background. Pediatric neuroectodermal malignancies express Nglycolylatedgangliosides including N-glycolyl GM3 (NeuGcGM3)as targets for immunotherapy. Procedure. We evaluated the toxicityand maximum tolerated dose and immunological response ofracotumomab, an anti-idiotype vaccine targeting NeuGcGM3through a Phase I study enrolling children with relapsed or resistanttumors expressing NeuGcGM3. Materials and methods. Drug dosewas escalated to three levels (0.15?0.25?0.4 mg) of racotumomabadministered intradermally. Each drug level included three patientsreceiving a total of three doses, every 14 days. A confirmation cohortwas added to the highest dose level. Antibody response was assessedupon study entry and at 4-week intervals for at least threeimmunological determinations for each patient. Results. Fourteenpatients were enrolled (10 with neuroblastoma, one withretinoblastoma, one with Wilms? tumor, and two with brainstemglioma). Three patients completed the three drug levels and threewere enrolled in the confirmation cohort. One patient died of tumorprogression before completing the three applications. Racotumomabwas well tolerated. The only side effect observed was grade 1?2toxicity at the injection site. Racotumomab elicited an IgM and/orIgG antibody response directed against NGcGM3 in nine patientsand IgM against racotumomab in 11 of 13 evaluable patients. Themaximum tolerated dose was not reached and no dose-limitingtoxicity was seen. Conclusions. Racotumomab vaccination has afavorable toxicity profile up to a dose of 0.4 mg, and most patientselicited an immune response. Its activity as immunotherapy forneuroectodermal malignancies will be tested in further clinical trials