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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04936529
Recruitment Status : Recruiting
First Posted : June 23, 2021
Last Update Posted : August 22, 2022
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 2, 2021
Estimated Primary Completion Date : June 15, 2023
Estimated Study Completion Date : June 15, 2023

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: QS-21




Primary Outcome Measures :
  1. Effect of GM-CSF on anti-GD2 antibody titers [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
  • 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04936529


Contacts
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Contact: Brian Kushner, MD 1-833-675-5437 kushnerb@mskcc.org
Contact: Fiorella Iglesias Cardenas, MD, MS 1-833-675-5437

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Brian Kushner, MD    833-675-5437      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Brian Kushner, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04936529    
Other Study ID Numbers: 21-206
First Posted: June 23, 2021    Key Record Dates
Last Update Posted: August 22, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Neuroblastoma
High-risk Neuroblastoma
OPT-821
QS-21
β-glucan
GM-CSF
Memorial Sloan Kettering Cancer Center
21-206
Additional relevant MeSH terms:
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Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue