Anti-GD2 3F8 Monoclonal Antibody and GM-CSF for High-Risk Neuroblastoma

Not Applicable

Completed

• Conditions: Neuroblastoma
• Interventions: Biological: Anti-GD2 3F8 Monoclonal Antibody; Drug: GM-CSF (granulocyte-macrophage colony-stimulating factor); Drug: oral isotretinoin

• Registration Number: NCT02100930
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary

The purpose of this study is to be able to supply an experimental combination of drugs called 3F8 and GM-CSF (also called sargramostim) to patients with high-risk neuroblastoma who may benefit from treatment.

Detailed Description

This treatment uses 3F8/GM-CSF and isotretinoin for: Group 1 patients are in 1st CR/VGPR; Group 2 patients are in a ≥2nd CR/VGPR; and Group 3 patients have primary refractory NB in BM. All patients will receive 3F8/GM-CSF through 24 months.

Road Map/Schema for Group 1 (1st CR/VGPR) and Group 2 (≥2nd CR/VGPR) patients:

Cycle 1 3F8 (iv) + GM-CSF subcutaneous (sc) (1 wk) 2-4-wk interval Cycle 2 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval\* - oral isotretinoin x14 days Cycle 3 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 4 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on Cycle 5 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) Cycle 6 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval Cycle 7 3F8 (iv) + GM-CSF (sc) (1 wk) Continue with 6-8-wk intervals through 24 months from 1st dose of 3F8. \* assessment of BM status by standard histology

Road Map/Schema for Group 3 patients (BM positive): The break between end of a cycle of 3F8/GM-CSF and start of next cycle is approximately 2-to-4-weeks through 4 cycles after achievement of CR in BM; subsequent breaks are \~6-8 weeks. Please see roadmap below for a patient achieving CR in BM after cycle 1. Cycle 1 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval\* - BM negative Cycle 2 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval\* - oral isotretinoin x14 days Cycle 3 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 4 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 5 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days Cycle 6 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) Cycle 7 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval Continue with 6-8-wk intervals through 24 months from 1st dose of 3F8.

\* assessment of BM response by standard histology

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-03-27
• Study First Submitted QC: 2014-03-27
• Study First Posted: 2014-04-01
• Primary Completion: 2019-03-07
• Study Completion: 2019-03-07
• Status Verified: 2019-04
• Results First Submitted: 2020-02-03
• Results First Submitted QC: 2020-02-17
• Last Update Submitted: 2020-02-17
• Results First Posted: 2020-02-28
• Last Update Posted: 2020-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

• Diagnosis of NB as defined by international criteria,62 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels.
• High-risk NB, as defined by risk-related treatment guidelines and the International NB Staging System, i.e., stage 4 with (any age) or without (>18 months) MYCNamplification, 63 or MYCN-amplified NB other than stage 1.64,65
• Patients are in CR/VGPR or have primary refractory NB in BM - i.e., NB resistant to standard therapy, as evidenced by persistence of NB in BM by histology or MIBG scan, but all other findings in scans show VGPR.
• Children and adults are eligible.
• Signed informed consent indicating awareness of the scheduling and side effects, as well as testing requirements, of this program.

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Exclusion Criteria

• Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity > or = to grade 3, except for grade 3 hematologic toxicity.
• Progressive disease (PD)
• History of allergy to mouse proteins.
• Active life-threatening infection.
• Human anti-mouse antibody (HAMA) titer >1000 Elisa units/ml.
• Pregnant women
• Inability to comply with protocol requirements.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neuroblastoma	Anti-GD2 3F8 Monoclonal Antibody	This is a single-arm, open label, open access study to provide the anti-GD2 murine IgG3 MoAb 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with high-risk neuroblastoma (NB). This immunotherapy has shown efficacy against minimal residual disease (MRD) in such patients.
Neuroblastoma	GM-CSF (granulocyte-macrophage colony-stimulating factor)	This is a single-arm, open label, open access study to provide the anti-GD2 murine IgG3 MoAb 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with high-risk neuroblastoma (NB). This immunotherapy has shown efficacy against minimal residual disease (MRD) in such patients.
Neuroblastoma	oral isotretinoin	This is a single-arm, open label, open access study to provide the anti-GD2 murine IgG3 MoAb 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with high-risk neuroblastoma (NB). This immunotherapy has shown efficacy against minimal residual disease (MRD) in such patients.

Primary Outcome Measures

Name	Time	Method
Therapeutic Response	2 years	Disease status is defined by the International Neuroblastoma Response Criteria - Complete response/remission (CR): NED; Partial response/remission: \>50% decrease in all disease parameters, exceptbone scan unchanged or improved; no more than 1 positive bone marrow site; Stable disease: \<50% decrease in all tumor markers; Progressive disease (PD): new lesion, or \>25 % increase in any disease marker.
Complete Remission	2 years	Disease status is defined by the International Neuroblastoma Response Criteria - Complete response/remission (CR): NED; Partial response/remission: \>50% decrease in all disease parameters, exceptbone scan unchanged or improved; no more than 1 positive bone marrow site; Stable disease: \<50% decrease in all tumor markers; Progressive disease (PD): new lesion, or \>25 % increase in any disease marker.

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States