Phase I trial of a bivalent gangliosides vaccine in combination with β-glucan for high-risk neuroblastoma in second or later remission Journal Article

Authors: Kushner, B. H.; Cheung, I. Y.; Modak, S.; Kramer, K.; Ragupathi, G.; Cheung, N. K. V.
Article Title: Phase I trial of a bivalent gangliosides vaccine in combination with β-glucan for high-risk neuroblastoma in second or later remission
Abstract: Purpose: To report on a phase I trial designed to find the maximally tolerated dose in children of the immunologic adjuvant OPT-821 in a vaccine containing neuroblastoma-associated antigens (GD2 andGD3; Clinicaltrials. govNCT00911560). Secondary objectives were to obtain preliminary data on immune response andactivity againstminimal residual disease (MRD). Treatment also includedthe immunostimulantβ-glucan. Experimental Design: Patients with neuroblastoma in 2nd complete/very good partial remission received vaccine subcutaneously (weeks 1-2-3-8-20-32-52). Vaccine contained 30 mg each of GD2 and GD3 stabilized as lactones and conjugated to the immunologic carrier protein keyhole limpet hemocyanin; and OPT-821, which was dose escalated as 50, 75, 100, and 150 mg/m2 per injection. Oral β-glucan (40 mg/kg/day, 14 days on/14 days off) started week 6. Results: The study was completed with 15 patients because there was no dose-limiting toxicity at 150 mg/m2 of OPT-821 (the dosing used in adults). Thirteen of fifteen patients received the entire protocol treatment, including 12 who remain relapse-free at 24 + to 39+ (median 32+) months and 1 who relapsed (single node) at 21 months. Relapse-free survival was 80% - 10% at 24 months. Vaccine and β-glucan were well tolerated. Twelve of fifteen patients had antibody responses against GD2 and/or GD3. Disappearance of MRD was documented in 6 of 10 patients assessable for response. Conclusions: This immunotherapy program lacks major toxicity and is transportable to any outpatient clinic. Patient outcome is encouraging but the efficacy is uncertain because of the complexity and heterogeneity of prior therapies. A larger phase II trial is underway. © 2014 AACR.
Keywords: child; clinical article; unclassified drug; drug tolerability; cancer recurrence; dose response; drug efficacy; cancer radiotherapy; temozolomide; cancer immunotherapy; multiple cycle treatment; clinical protocol; tumor antigen; high risk patient; irinotecan; drug dose escalation; cancer regression; immune response; cancer vaccine; neuroblastoma; ganglioside gd2; minimal residual disease; antibody response; immunological adjuvant; immunostimulation; maximum tolerated dose; beta glucan; drug conjugation; drug stability; ganglioside gd3; hemocyanin; recurrence free survival; phase 1 clinical trial (topic); lactone; human; priority journal; article; opt 821
Journal Title: Clinical Cancer Research
Volume: 20
Issue: 5
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2014-03-01
Start Page: 1375
End Page: 1382
Language: English
DOI: 10.1158/1078-0432.ccr-13-1012
PROVIDER: scopus
PUBMED: 24520094
PMCID: PMC5592799
Notes: Export Date: 1 August 2014 -- CODEN: CCREF -- Source: Scopus
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MSK Authors
  1. Brian Kushner
    190 Kushner
  2. Nai-Kong Cheung
    439 Cheung
  3. Kim Kramer
    168 Kramer
  4. Shakeel Modak
    159 Modak
  5. Govindaswami Ragupathi
    133 Ragupathi
  6. Irene Y Cheung
    73 Cheung