Vaccine + β-glucan + GM-CSF for Neuroblastoma
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Disqualifiers: Severe organ dysfunction, Allergy to GM-CSF, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of the study is to explore the combination of a bivalent vaccine, a sugar called beta-glucan (β-glucan), and a protein called granulocyte-macrophage colony stimulating factor (GM-CSF) as an effective treatment for people with high-risk neuroblastoma that is in complete remission. The combination may be effective because the different parts of the treatment work to strengthen the immune system's response against cancer cells in different ways.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, prior treatment with other immunotherapy must be completed at least 21 days before the first vaccination, and investigational therapy must be completed at least 28 days before.
What data supports the effectiveness of the treatment Vaccine + β-glucan + GM-CSF for Neuroblastoma?
Research shows that β-glucan, when used with a ganglioside vaccine, can boost the immune response in patients with high-risk neuroblastoma, which is linked to better survival. Additionally, GM-CSF has shown antitumor effects in neuroblastoma treatment in mice, suggesting potential benefits in humans.
12345Is the combination of Vaccine, β-glucan, and GM-CSF safe for treating neuroblastoma?
The combination of β-glucan and GM-CSF has been studied for safety in patients with neuroblastoma. In one study, the treatment was generally well tolerated, but some patients experienced severe low platelet counts (thrombocytopenia), which improved with treatment. Overall, the treatment showed potential for safety, but further investigation is needed.
23456What makes the Vaccine + β-glucan + GM-CSF treatment unique for neuroblastoma?
This treatment is unique because it combines a vaccine with β-glucan, which enhances the immune response, and GM-CSF, which stimulates white blood cell production, to target neuroblastoma. This approach aims to boost the body's immune system to fight cancer cells more effectively, unlike traditional treatments that primarily focus on directly killing cancer cells.
23457Eligibility Criteria
This trial is for people with high-risk neuroblastoma in complete remission. Participants must have a confirmed diagnosis, be within certain time frames post-therapy, and have adequate organ function. Pregnant individuals or those with severe allergies to the study drugs, significant organ dysfunction, or life-threatening infections cannot join.Inclusion Criteria
My neuroblastoma diagnosis is confirmed by lab tests and high urine catecholamine levels.
My neuroblastoma is high-risk based on specific genetic features and its spread.
Prior treatment with other immunotherapy, including mAbs or vaccine, is allowed but must be completed ≥ 21 days before the 1st vaccination. Note: Prior treatment with an investigational therapy must be completed ≥ 28 days before the 1st vaccination. ≥ 21 and ≤ 180 days between completion of systemic therapy and 1st vaccination. Patients have recovered from any toxicities grade 3 or higher caused by prior therapies. Patients with history of allergy to GM-CSF or who are unable to obtain GM-CSF because of insurance issues are eligible but will be assigned to Group 3 (no GM-CSF exploratory arm). Patients previously enrolled on this trial are eligible for repeat enrollment if they did not complete all vaccine injections during the first time on protocol but they will be assigned to Group 3 and will not be included in the primary biostatistical analyses. A negative pregnancy test is required for patients with child-bearing capability. Signed informed consent indicating awareness of the investigational nature of this program
+2 more
Exclusion Criteria
My major organs are functioning well, without severe issues.
I am currently being treated for a severe infection.
History of allergy to KLH, QS-21, OPT-821, or glucan
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a combination of a bivalent vaccine, oral β-glucan, and GM-CSF (for some groups) with booster vaccinations at specified weeks
156 weeks
Multiple visits for vaccinations and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
32 weeks
Participant Groups
The study tests a combination of a bivalent vaccine with β-glucan (a sugar) and GM-CSF (a protein) to boost the immune system against neuroblastoma cancer cells. The treatment aims to improve the body's natural defense by using different mechanisms.
3Treatment groups
Experimental Treatment
Group I: Group 3Experimental Treatment2 Interventions
Group 3 will include participants who cannot be randomized (e.g., due to allergy to GMCSF). It will also include participants previously treated with this vaccine and oral β-glucan on the predecessor MSK protocol IRB# 05-075 or on this protocol (participants can therefore be enrolled more than one time on this protocol). These participants will be treated as in Group 1. Participants who are registered to Group 3 and have been previously treated with vaccine (in this protocol or MSK predecessor 05-075) will not receive vaccines 4 and 6. These patients will receive a total of 8 injections. The analyses in this group will be exploratory.
Group II: Group 2Experimental Treatment3 Interventions
Group 2 participants receive oral β-glucan (40 mg/kg/day) starting week 1. Participants also receive GM-CSF (250 mcg/m2/day) x3 days with vaccinations #1-#3; x7 days with vaccinations #4-#9; and x5 days with vaccination #10. The treatment includes annual booster vaccinations, with a 2-week cycle of β-glucan, administered at weeks 8, 20, 32, 52, 78, 104, and 156 (vaccinations #1 \& #4-10)
Group III: Group 1Experimental Treatment2 Interventions
Group 1 participants receive oral β-glucan (40 mg/kg/day x 14 days) starting week 1. This schedule includes annual booster vaccinations, with β-glucan, administered at weeks 8, 20, 32, 52, 78, 104, and 156 (vaccinations #1 \& #4-10). Participants will not receive GM-CSF.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Cancer CenterNew York, NY
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
A phase 1/2 study of autologous neuroblastoma tumor cells genetically modified to secrete IL-2 in patients with high-risk neuroblastoma. [2018]Autologous neuroblastoma (NB) tumor cells modified to secrete interleukin (IL)-2 (auto-IL-2) can be safely given to patients with advanced neuroblastoma and generate antitumor immune responses. As the benefits of tumor immunization may be greater in patients with minimal residual disease and thus rely on surrogate markers such as immune responses to measure effect, we studied the frequency of immune changes associated with vaccination. Thirteen patients (8 in first remission and 5 after treatment for recurrent NB) received 5 to 8 subcutaneous injections of auto-IL-2 at 0.3 x 10 cells/kg. The vaccine was well tolerated. Injection site biopsies revealed increased cellularity caused by infiltration of CD4 and CD8 lymphocytes, eosinophils, and dendritic cells. Enzyme-linked immunosorbent spot assays for interferon-gamma and IL-5 demonstrated that vaccination produced a rise in circulating CD4 and CD8 T cells responsive to stimulation by autologous tumor cells. Median event-free survival was 22 months for patients in first remission and 3 months for all others. Four patients treated in first remission remain alive and 3 without disease recurrence.
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.
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.
Effects of irradiated tumor vaccine and continuous localized infusion of granulocyte-macrophage colony-stimulating factor on neuroblastomas in mice. [2019]Immunomodulatory treatment has been proposed as a feasible strategy for neuroblastoma treatment. In this study, the antitumor effects of a continuous localized subcutaneous infusion of granulocyte-macrophage colony-stimulating factor (GM-CSF) into the injection site of irradiated tumor vaccine used as a source of tumor antigens on mouse neuroblastoma were investigated.
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.
A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. [2021]Evaluate the clinical safety, toxicity, immune activation/modulation, and maximal tolerated dose of hu14.18-IL2 (EMD 273063) in pediatric patients with recurrent/refractory neuroblastoma and other GD2-positive solid tumors.
Antitumor vaccine effect of irradiated murine neuroblastoma cells producing interleukin-2 or granulocyte macrophage-colony stimulating factor. [2019]We have examined vaccination effects of cytokine-producing murine neuroblastoma cells (C1300). C1300 cells retrovirally transduced with interleukin-2 (IL-2) or granulocyte macrophage-colony stimulation factor (GM-CSF) gene were established. Their in vitro proliferation rates and the class I expression of major histocompatibility complex were not different from those of wild-type cells. Five-Gy irradiation of the respective cytokine producers slightly reduced the in vitro cell growth but treatment with 15 Gy significantly impaired the proliferation. In contrast, the secretion of both cytokines from the respective transduced cells was retained compared with the cell growth. We immunized syngeneic mice with irradiated wild-type cells as a control or cytokine-producing cells and challenged the mice with unirradiated wild-type cells. The control mice developed tumors of the challenged wild-type cells, on the contrary, the mice which had received irradiated IL-2 or GM-CSF producers did not. Thus, IL-2- or GM-CSF-expressing syngeneic tumor cells can be potentially used as a tumor vaccine by inducing protective immunity against low immunogenic neuroblastomas in the inoculated hosts.