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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04936529

Collaborator

(none)

132

Enrollment

Location

Arms

22.4

Anticipated Duration (Months)

5.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma	Dietary Supplement: β-glucan Drug: GM-CSF Biological: OPT-821	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

132 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 2, 2021

Anticipated Primary Completion Date :

Jun 15, 2023

Anticipated Study Completion Date :

Jun 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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 cycle after vaccination #7, then 1 cycle with each subsequent vaccination (#8-#14). Group 3 participants will be treated as in Group 1. Other Names: oral β-glucan 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. Other Names: QS-21
Experimental: 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)	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 cycle after vaccination #7, then 1 cycle with each subsequent vaccination (#8-#14). Group 3 participants will be treated as in Group 1. Other Names: oral β-glucan 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. Other Names: QS-21
Experimental: 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.	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 cycle after vaccination #7, then 1 cycle with each subsequent vaccination (#8-#14). Group 3 participants will be treated as in Group 1. Other Names: oral β-glucan 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. Other Names: QS-21

Arm

Intervention/Treatment

Experimental: 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.

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 cycle after vaccination #7, then 1 cycle with each subsequent vaccination (#8-#14). Group 3 participants will be treated as in Group 1.

Other Names:

oral β-glucan

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.

Other Names:

QS-21

Experimental: 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)

Dietary Supplement: β-glucan

Other Names:

oral β-glucan

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

Other Names:

QS-21

Experimental: 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.

Dietary Supplement: β-glucan

Other Names:

oral β-glucan

Biological: OPT-821

Other Names:

QS-21

Outcome Measures

Primary Outcome Measures

Effect of GM-CSF on anti-GD2 antibody titers [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.
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

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 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 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.