Phase II Trial of a Bivalent Vaccine With the Immunological Adjuvant OPT-821 (QS-21), in Combination With Oral β-glucan and Randomization of GM-CSF, for High-risk Neuroblastoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 286
- 试验地点
- 1
- 主要终点
- Effect of GM-CSF on anti-GD2 antibody titers
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the MSK Department of Pathology) or BM metastases plus high urine catecholamine levels or positivity in MIBG scan
- •HR-NB as defined by risk-related treatment guidelines and international criteria,i.e., metastatic/non-localized disease with MYCN amplification (any age), MYCN-non-amplified metastatic disease >18 months old, MYCNamplified localized disease (any age), or disease resistant to standard chemotherapy.
- •HR-NB (as defined above) and in 1) first CR at ≥ 6 months from initiation of immunotherapy using anti-GD2 antibody, or 2) second or subsequent CR (achieved after treatment for PD). CR is defined according to the International Neuroblastoma Response Criteria.Patients with positive MIBG scan but negative FDG-PET scan, and CR in BM, are eligible. For those patients with a positive MIBG scan, the negative FDG-PET scan can be per PI discretion to repeat within the 45 day window period prior to enrollment.
- •Patients with grade 3 toxicities or less using the Common Toxicity Criteria (Version 5.0) developed by the National Cancer Institute of the USA (CTCAE v5.0) related to hematologic, cardiac, neurological, pulmonary, renal, hepatic or gastrointestinal function as determined by blood tests or physical exam.
- •Hematologic Function
- •Absolute neutrophil count (ANC) ≥ 500/mcl
- •Absolute lymphocyte count ≥ 500/mcl
- •Hemaglobin (Hgb) ≥ 8 g/dL
- •Platelet count ≥ 50,000 mm^3
- •Renal Function o Serum creatinine ≤ 3.0 x ULN
- •eGFR >60 mL/min/1.73 m^2
- •- Hepatic Function
- •Serum bilirubin ≤ 3.0 × ULN
- •Aspartate transaminase (AST) ≤ 5.0 × ULN
- •Alanine aminotransferase (ALT) ≤ 5.0 × ULN
- •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 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 w ith child-bearing capability.
- •Signed informed consent indicating awareness of the investigational nature of this program.
排除标准
- •Patients w ith significant (grade >4) hematologic, cardiac, neurological, pulmonary, renal, hepatic or gastrointestinal function as determined by blood tests or physical exam, using the Common Toxicity Criteria (Version 5.0) developed by the National Cancer Institute of the USA (CTCAE v5.0)
- •History of allergy to KLH, QS-21, OPT-821, or glucan.
- •Active life-threatening infection requiring systemic therapy.
- •Inability to comply with protocol requirements.
- •Patients with history of allergy to GM-CSF or who are unable to obtain GM-CSF because of insurance issues are ineligible
研究组 & 干预措施
Group 2
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)
干预措施: OPT-821 (Biological)
Group 3
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.
干预措施: OPT-821 (Biological)
Group 2
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)
干预措施: GM-CSF (Drug)
Group 1
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.
干预措施: β-glucan (Dietary Supplement)
Group 2
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)
干预措施: β-glucan (Dietary Supplement)
Group 3
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.
干预措施: β-glucan (Dietary Supplement)
Group 1
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.
干预措施: OPT-821 (Biological)
结局指标
主要结局
Effect of GM-CSF on anti-GD2 antibody titers
时间窗: 32 weeks
Effect of GM-CSF on anti-GD2 antibody titers among patients who are in first or second (or later) CR, i.e., have no evidence of NB by standard studies.
次要结局
未报告次要终点