Clinical trial NCT04936529: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: Neuroblastoma
High-risk Neuroblastoma
OPT-821
QS-21
β-glucan
GM-CSF
Memorial Sloan Kettering Cancer Center
21-206
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2021-06-23
Enrollment: 286
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: Effect of GM-CSF on anti-GD2 antibody titers
timeFrame: 32 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Brian Kushner, MD
role: PRINCIPAL_INVESTIGATOR
References: