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.
Recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| GM-CSF | Group 2 | |
| OPT-821 | QS-21 | Group 1 |
| Name | Type | Description | Interventions |
|---|---|---|---|
| Group 1 | Experimental | 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). Participants will not receive GM-CSF. |
|
| Group 2 | Experimental | 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). Participants also receive GM-CSF (250 mcg/m2/day) x3 days with vaccinations #1-#3; x7 days with vaccinations #8-#11; and x5 days with vaccinations #12-#14. The treatment 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 3 | Experimental | 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. The analyses in this group will be exploratory. |
|
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.
- Absolute lymphocyte count >500/mcl and absolute neutrophil count ≥ 500/mcl.
- 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
cardiac, neurological, pulmonary, renal, hepatic or gastrointestinal function as
determined by blood tests or physical exam.
- Prior treatment with other immunotherapy, including mAbs or vaccine, is allowed but
must be completed ≥ 21 days before the 1st vaccination.
- ≥ 21 and ≤ 180 days between completion of systemic therapy and 1st vaccination.
- 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 but will
be assigned to Group 3 and will not be included in the primary biostatistical
analyses.
- Signed informed consent indicating awareness of the investigational nature of this
program.
Exclusion Criteria:
- History of allergy to KLH, QS-21, OPT-821, or glucan.
- Active life-threatening infection.
- Inability to comply with protocol requirements.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | N/A |
| Eligible Gender: | All |
| Healthy Volunteers: | Accepts Healthy Volunteers |
| Measure: | Effect of GM-CSF on anti-GD2 antibody titers |
| Time Frame: | 32 weeks |
| Safety Issue: | |
| Description: | 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. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Memorial Sloan Kettering Cancer Center |
August 10, 2021
