Vaccine + Beta-glucan for Neuroblastoma
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Disqualifiers: Grade 4 toxicities, Allergy, Infection, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to test which treatment schedule of β-glucan with bivalent vaccine is more effective for participants with high-risk neuroblastoma that is in complete remission.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.
What evidence supports the effectiveness of the treatment combining a vaccine and beta-glucan for neuroblastoma?
Research shows that oral beta-glucan, when used with a GD2/GD3 ganglioside vaccine, can stimulate an antibody response in patients with high-risk neuroblastoma, which is linked to improved survival. Additionally, a study found that combining beta-glucan with an anti-GD2 antibody showed antineoplastic (cancer-fighting) activity in patients with advanced-stage neuroblastoma.
12345Is the combination of Vaccine and Beta-glucan safe for treating neuroblastoma?
The combination of Vaccine and Beta-glucan has been generally well-tolerated in clinical trials for neuroblastoma, with most patients experiencing no severe side effects. However, in one study, two patients developed severe low platelet counts (thrombocytopenia) at higher doses, which improved with treatment. Overall, the treatment shows a favorable safety profile.
12346How is the Vaccine + Beta-glucan treatment for neuroblastoma different from other treatments?
This treatment is unique because it combines a bivalent vaccine targeting specific neuroblastoma antigens (GD2 and GD3) with beta-glucan, an immune-boosting substance, to enhance the body's immune response against the cancer. Unlike traditional treatments, this approach aims to stimulate the immune system to fight the cancer more effectively.
12478Eligibility Criteria
This trial is for people with high-risk neuroblastoma in complete remission. Participants must have a certain level of lymphocytes and neutrophils, be within specific time frames post-therapy, and able to consent. Pregnant individuals or those with severe organ dysfunction, allergies to the vaccine components, or inability to follow protocol are excluded.Inclusion Criteria
Your absolute lymphocyte count is 500/mcl or higher.
Patients with the potential to bear children must provide a negative pregnancy test.
Absolute neutrophil count (ANC) ≥ 500/mcl
+6 more
Exclusion Criteria
My blood tests and physical exams show no severe issues with my heart, lungs, kidneys, liver, or blood.
I have previously received this vaccine.
I do not have a severe infection needing treatment through my veins.
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive oral β-glucan and bivalent vaccine. Group 1 receives β-glucan for 14 days on, 14 days off for ~20 weeks, then one 14-day cycle with each of vaccinations #6-#10. Group 2 continues until vaccination #7 (~52 weeks), then one 14-day cycle with each of vaccinations #8-#10.
52 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study is testing different treatment schedules of β-glucan combined with a bivalent vaccine (OPT-821/QS-21) on patients who have high-risk neuroblastoma but are currently in complete remission. The goal is to find out which schedule might be more effective.
2Treatment groups
Experimental Treatment
Group I: Group 2Experimental Treatment2 Interventions
Participants will receive oral β-glucan (40 mg/kg/day) for 14 days on, and 14 days off, beginning with vaccination #1 and continuing until vaccination #7 (\~52 weeks), then only one 14-day cycle with each of vaccinations #8-#10.
Group II: Group 1Experimental Treatment2 Interventions
Participants will receive oral β-glucan (40 mg/kg/day) for 14 days on, and 14 days off, beginning with vaccination #1 and continuing until vaccination #5 (\~20 weeks), then only one 14-day cycle with each of vaccinations #6-#10.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Westchester (Consent only)Harrison, NY
Memorial Sloan Kettering at Basking Ridge (Consent only)Basking Ridge, NJ
Memorial Sloan Kettering Monmouth (Consent Only)Middletown, NJ
Memorial Sloan Kettering Bergen (Consent Only)Montvale, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
Anti-GD2 antibody 3F8 and barley-derived (1 → 3),(1 → 4)-β-D-glucan: A Phase I study in patients with chemoresistant neuroblastoma. [2021]β-glucans are complex, naturally-occurring polysaccharides that prime leukocyte dectin and complement receptor 3. Based on our preclinical findings, indicating that oral barley-derived (1 → 3),(1 → 4)-β-D-glucan (BG) synergizes with the murine anti-GD2 antibody 3F8 against neuroblastoma, we conducted a Phase I clinical study to evaluate the safety of this combinatorial regimen in patients affected by chemoresistant neuroblastoma. In this setting, four cohorts of six heavily pre-treated patients bearing recurrent or refractory advanced-stage neuroblastoma were treated with 3F8 plus BG. Each cycle consisted of intravenous 3F8 at a fixed dose of 10 mg/m2/day plus concurrent oral BG, dose-escalated from 10 to 80 mg/Kg/day, for 10 d. Patients who did not develop human anti-mouse antibodies could be treated for up to 4 cycles. Twenty-four patients completed 50 cycles of therapy. All patients completed at least one cycle and were evaluable for the assessment of toxicity and responses. The maximum tolerated dose of BG was not reached, but two patients developed dose-limiting toxicities. These individuals developed grade 4 thrombocytopenia after one cycle of BG at doses of 20 mg/Kg/day and 40 mg/Kg/day, respectively. Platelet counts recovered following the administration of idiopathic thrombocytopenic purpura therapy. There were no other toxicities of grade > 2. Eleven and 13 patients manifested stable and progressive disease, respectively. Thirteen out of 22 patients with pre-treatment positive 123I-MIBG scans demonstrated clinical improvement on semiquantitative scoring. Responses did not correlate with BG dose or with in vitro cytotoxicity. In summary, 3F8 plus BG is well tolerated and shows antineoplastic activity in recurrent or refractory advanced-stage neuroblastoma patients. Further clinical investigation of this novel combinatorial immunotherapeutic regimen is warranted.
Phase I trial of a bivalent gangliosides vaccine in combination with β-glucan for high-risk neuroblastoma in second or later remission. [2021]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 and GD3; Clinicaltrials.gov NCT00911560). Secondary objectives were to obtain preliminary data on immune response and activity against minimal residual disease (MRD). Treatment also included the immunostimulant β-glucan.
Survival Impact of Anti-GD2 Antibody Response in a Phase II Ganglioside Vaccine Trial Among Patients With High-Risk Neuroblastoma With Prior Disease Progression. [2022]Anti-GD2 monoclonal antibody (mAb) has proven efficacy in high-risk neuroblastoma (HR-NB). A small phase I GD2/GD3 vaccine trial (n = 15) described long-term survival and a favorable safety profile among patients with a history of disease progression (PD). The kinetics of mounting antibody response to vaccine and its prognostic impact on survival are now investigated in a phase II study (ClinicalTrials.gov identifier: NCT00911560).
Effect of Oral β-Glucan on Antibody Response to Ganglioside Vaccine in Patients With High-Risk Neuroblastoma: A Phase 2 Randomized Clinical Trial. [2023]Among patients with high-risk relapsed metastatic neuroblastoma, oral β-glucan adjuvant during GD2/GD3 ganglioside vaccine boost has stimulated IgG antibody response, which was associated with improved survival; however, the effectiveness of oral β-glucan during the vaccine priming phase remains unproven.
[Anti-GD2 antibodies in treatment of high-risk Neuroblastoma: present and perspectives]. [2022]Neuroblastoma is the most frequent extra-cranial pediatric solid tumor, occurring in young children, 90% being less than 5 years at diagnosis. It remains a therapeutic challenge since survival of high-risk neuroblastoma patients that represent around 50% of the patients is around 50% in spite of extensive combined treatments. Immunotherapy based on the use of antibodies directed to GD2, a ganglioside strongly expressed by almost all neuroblastoma cells, has been developed during the last decade. In SIOPEN studies have shown that dinatuximab beta (Qarziba®) is effective on refractory/relapsed patients and improves survival when administered in the first line maintenance treatment. Other strategies are currently explored using combination with chemotherapy at relapse and evaluating the benefits of an earlier administration during the induction treatment. In addition, more selective antibodies are also developed to decrease toxicity, especially neuropathic pain that is one of the major toxic effect.
Immune Response and Outcome of High-Risk Neuroblastoma Patients Immunized with Anti-Idiotypic Antibody Ganglidiomab: Results from Compassionate-Use Treatments. [2022](1) Background: High-risk neuroblastoma (HR-NB) is associated with a poor prognosis despite a multimodal high-intensity treatment regimen, including immunotherapy with anti-GD2 monoclonal antibodies (mAb). Here, we investigated the effects of an anti-idiotypic vaccine based on the mAb ganglidiomab that structurally mimics GD2. (2) Methods: Patients with HR-NB treated with anti-GD2 mAb dinutuximab beta and who achieved complete remission after frontline or salvage therapy were offered the vaccine (0.5 mg ganglidiomab adsorbed to Alhydrogel®). Side effects (CTCAE v4.03) and immune responses were determined on each visit. We also evaluated the time to relapse or progression until the last follow-up. (3) Results: Seven HR-NB patients (five frontlines, two relapsed) received 6-22 subcutaneous injections every two weeks. Six of the seven patients showed an immune response. The non-responding patient had a haploidentical stem cell transplantation as part of the previous treatment. No fever, pain, neuropathy, or toxicities ≥ grade 3 occurred during or post-treatment. All immunized patients did not experience relapses or progressions of their neuroblastoma. (4) Conclusions: This is the first-in-man use of the ganglidiomab vaccine, which was well-tolerated, and all patients not pre-treated by haploidentical transplantation developed vaccine-specific immune responses. These findings provide an important basis for the design of prospective clinical trials.
Phase I Trial of Oral Yeast-Derived β-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma. [2022]Beta glucans, complex polysaccharides, prime leukocyte dectin-1 and CR3-receptors and enhance anti-tumor cytotoxicity of complement-activating monoclonal antibodies. We conducted a phase I study (clinicaltrials.gov NCT00492167) to determine the safety of the combination of yeast-derived beta glucan (BG) and anti-GD2 murine monoclonal antibody 3F8 in patients with relapsed or refractory high-risk neuroblastoma. Patients received intravenous 3F8 (fixed dose of 10 mg/m2/day × 10 days) and oral BG (dose-escalated from 10-200 mg/kg/day × 17 days in cohorts of 3-6 patients each). Forty-four patients completed 141 cycles. One patient developed DLT: transient self-limiting hepatic transaminase elevation 5 days after starting BG (120 mg/kg/day). Overall, 1, 3, 12 and 24 evaluable patients had complete response, partial response, stable and progressive disease, respectively, at the end of treatment. Positive human anti-mouse antibody response and dectin-1 rs3901533 polymorphism were associated with better overall survival. BG dose level and serum BG levels did not correlate with response. Progression-free and overall survival at 2 years were 28% and 61%, respectively. BG lacked major toxicity. Treatment with 3F8 plus BG was associated with anti-neuroblastoma responses in patients with resistant disease. Although the maximal tolerated dose for yeast BG was not reached, considering the large volume of oral BG, we recommended 40 mg/kg/day as the phase II dose.
Induction of protective immune responses against NXS2 neuroblastoma challenge in mice by immunotherapy with GD2 mimotope vaccine and IL-15 and IL-21 gene delivery. [2018]The GD2 ganglioside expressed on neuroectodermal tumor cells is weakly immunogenic in tumor-bearing patients and induces predominantly IgM antibody responses in the immunized host. Using a syngeneic mouse challenge model with GD2-expressing NXS2 neuroblastoma, we investigated novel strategies for augmenting the effector function of GD2-specific antibody responses induced by a mimotope vaccine. We demonstrated that immunization of A/J mice with DNA vaccine expressing the 47-LDA mimotope of GD2 in combination with IL-15 and IL-21 genes enhanced the induction of GD2 cross-reactive IgG2 antibody responses that exhibited cytolytic activity against NXS2 cells. The combined immunization regimen delivered 1 day after tumor challenge inhibited subcutaneous (s.c.) growth of NXS2 neuroblastoma in A/J mice. The vaccine efficacy was reduced after depletion of NK cells as well as CD4(+) and CD8(+) T lymphocytes suggesting involvement of innate and adaptive immune responses in mediating the antitumor activity in vivo. CD8(+) T cells isolated from the immunized and cured mice were cytotoxic against syngeneic neuroblastoma cells but not against allogeneic EL4 lymphoma, and exhibited antitumor activity after adoptive transfer in NXS2-challenged mice. We also demonstrated that coimmunization of NXS2-challenged mice with the IL-15 and IL-21 gene combination resulted in enhanced CD8(+) T cell function that was partially independent of CD4(+) T cell help in inhibiting tumor growth. This study is the first demonstration that the mimotope vaccine of a weakly immunogenic carbohydrate antigen in combination with plasmid-derived IL-15 and IL-21 cytokines induces both innate and adaptive arms of the immune system leading to the generation of effective protection against neuroblastoma challenge.