A Study of a Vaccine in Combination With β-glucan and GM-CSF in People With Neuroblastoma

Official title

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

Overview

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.

Interventions

• Dietary supplement β-glucan
  Group 1 participants receive oral β-glucan (40 mg/kg/day) starting week 1 and continue with \~2 weeks on, \~2 weeks off, up to 1 cycle after vaccination #7, then 1 cycle with each subsequent vaccination (#8-#14). This schedule includes annual booster vaccinations, with a 2-week cycle of β-glucan, administered at months 36 (3 years), 48 (4 years), and 60 (5 years). Group 2 participants receive oral β-glucan (40 mg/kg/day) starting week 1 and continue with \~2 weeks on, \~2 weeks off, up to 1 cyc
• Drug GM-CSF
  Group 1 participants will not receive GM-CSF. Group 2 participants will receive GM-CSF (250 mcg/m2/day) x3 days with vaccinations #1-#3; x7 days with vaccinations #4-#11; and x5 days with vaccinations #12-#14. Group 3 participants will be treated as in Group 1.
• Biological OPT-821
  Vaccine injections must occur a minimum of 6 days apart. After the first four vaccine injections, vaccines can be administered up to two weeks earlier or later than indicated without representing a protocol violation.

Primary outcome measures

• Effect of GM-CSF on anti-GD2 antibody titers [Time frame: 32 weeks]

Eligibility criteria

Inclusion criteria

• 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.
• 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

or

• 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.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Factorial

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Memorial Sloan Kettering Cancer Center — New York

Identifiers

NCT: NCT04936529 · 21-206

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗