A Phase 2 interventional study of anti-GD2 murine IgG3 monoclonal antibody 3F8 and anti-GD2 murine IgG3 monoclonal antibody 3F8 in Neuroblastoma, sponsored by Memorial Sloan Kettering Cancer Center. Completed at 1 site in United States. Per ClinicalTrials.gov, last updated 2022-05-16.
Sponsored by Memorial Sloan Kettering Cancer Center · Phase 2, Interventional, and Treatment
RATIONALE: Monoclonal antibodies, such as monoclonal antibody 3F8, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Combining monoclonal antibody 3F8 with sargramostim may cause a stronger immune response and kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combining monoclonal antibody 3F8 with sargramostim in treating patients who have neuroblastoma.
OBJECTIVES:
OUTLINE: This is an open-label study. Patients are stratified according to evaluable disease (yes [primary refractory bone marrow disease] vs no [no evidence of disease]).
Patients receive sargramostim (GM-CSF) subcutaneously on days -5 to 4 and monoclonal antibody 3F8 IV over 0.5-1.5 hours on days 0-4. Treatment repeats every 3 weeks for 4 courses and then every 8 weeks for up to a total of 24 months in the absence of disease progression or unacceptable toxicity.
Beginning after 2 courses of GM-CSF and monoclonal antibody 3F8, patients also receive oral isotretinoin twice daily on days 1-14 (when no monoclonal antibody 3F8 is administered). Treatment with isotretinoin repeats approximately every 28 days for 6 courses.
PROJECTED ACCRUAL: A total of 340 patients will be accrued for this study.
625 studies on the registry are indexed under Neuroblastoma; 122 are open to participants now.
This study's enrollment of 291 is above the median of 32 across 475 interventional studies indexed under Neuroblastoma.
Browse Neuroblastoma studies →Memorial Sloan Kettering Cancer Center is the lead sponsor of 1,930 studies on the registry; 328 are open to participants now.
Of its 129 completed or terminated interventional studies of FDA-regulated products, 66 (51%) have results posted.
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DISEASE CHARACTERISTICS:
Disease must meet risk-related treatment guidelines and any of the following International Neuroblastoma Staging System stages:
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
This phase II trial of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response of minimal residual disease (MRD) in patients with high-risk neuroblastoma (NB) and help establish the optimal way to use GM-CSF.
Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8
This phase II trial of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response of minimal residual disease (MRD) in patients with high-risk neuroblastoma (NB) and help establish the optimal way to use GM-CSF.
Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8
The total dosage of 3F8 per cycle is the same as in prior trials (100 mg/m2), administered at 20 mg/m2/day and infused over \~1.5 hr or less (0.5 hr is customary), with analgesics and antihistamines used as needed for expected side-effects. 3F8 is started \~1 hr after completion of GM-CSF administration. GM-CSF is dosed at 250 mcg/m2/day from day -5 to day +1 (Wednesday to Tuesday is customary) , and is 500 mcg/m2/day thereafter (i.e., on days +2 to +4; Wednesday to Friday), as in the predecessor protocol.18,74 Patients come off study if progressive disease occurs or if there is life-threatening grade 4 toxicity from 3F8; otherwise, patients will receive a minimum of 4 cycles of treatment and will continue treatment through 24 months. It is expected that patients will receive \~10 cycles.
Also known as: patients (enrolled on study for treatment of primary refractory disease), the, break between end of a cycle of 3F8/GM-CSF and start of next cycle is 2-to-4-weeks through 4, cycles after achievement of CR in BM; subsequent breaks are ~8 weeks. In this, group, isotretinoin is started after documentation of response to, and after, >2 cycles of, 3F8/GM-CSF.
The total dosage of 3F8 per cycle is the same as in prior trials (100 mg/m2), administered at 20 mg/m2/day and infused over \~1.5 hr or less (0.5 hr is customary), with analgesics and antihistamines used as needed for expected side-effects. 3F8 is started \~1 hr after completion of GM-CSF administration. GM-CSF is dosed at 250 mcg/m2/day from day -5 to day +1 (Wednesday to Tuesday is customary) , and is 500 mcg/m2/day thereafter (i.e., on days +2 to +4; Wednesday to Friday), as in the predecessor protocol.18,74 Patients come off study if progressive disease occurs or if there is life-threatening grade 4 toxicity from 3F8; otherwise, patients will receive a minimum of 4 cycles of treatment and will continue treatment through 24 months. It is expected that patients will receive \~10 cycles.
Also known as: For Group 2 patients (enrolled on study in CR/VGPR, i.e., with no evidence of disease),, the break between end of a cycle and start of next cycle is 2-to-4 weeks through 4 cycles;, subsequent breaks are ~8 weeks. Isotretinoin is started after cycle 2 of 3F8/GM-CSF. Road, map/schema is in section 4.2. Regarding patients in second or greater CR from relapse in the, central nervous system, if they develop early HAMA which precludes timely completion of the, minimum of 4 cycles of 3F8/GM-CSF, they are eligible to go off protocol, to be treated with, low-dose maintenance regimens of irinotecan,94 temozolomide,95 or the two agents combined;96, they can resume treatment with 3F8/GM-CSF if HAMA becomes negative.
Efficacy at Completion of Treatment
Time frame: 3 years
Relapse-free Survival Every 3 Months
Time frame: 3 years
Compare Granulocyte Activation in Patients Treated With Short-term vs Prolonged Daily Exposure to Sargramostim (GM-CSF) After 4 Courses
Time frame: 3 years
Simplify Treatment With Consequent Reduction in Cost
Time frame: 3 years
| Milestone | Participants With Refractory Bone Marrow Disease and High Risk of Recurrence |
|---|---|
| Started | 291 |
| Completed | 291 |
| Not completed | 0 |
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Collected over 2 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Participants With Refractory Bone Marrow Disease and High Risk of Recurrence | 135/291 (46.4%) | 153/291 (52.6%) | 287/291 (98.6%) |
| Event | Participants With Refractory Bone Marrow Disease and High Risk of Recurrence |
|---|---|
| FeverGeneral disorders | 121/291 |
| Infection w.out neutropeniaInfections and infestations | 57/291 |
| Rigors, chillsGeneral disorders | 18/291 |
| VomitingGastrointestinal disorders | 16/291 |
| HypertensionVascular disorders | 12/291 |
| Allergic Reaction/HyperImmune system disorders | 11/291 |
| Febrile neutropeniaBlood and lymphatic system disorders | 11/291 |
| HypotensionVascular disorders | 10/291 |
| HypokalemiaMetabolism and nutrition disorders | 9/291 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 9/291 |
| Event | Participants With Refractory Bone Marrow Disease and High Risk of Recurrence |
|---|---|
| Pain, otherGeneral disorders | 157/291 |
| UrticariaSkin and subcutaneous tissue disorders | 142/291 |
| FlushingVascular disorders | 103/291 |
| PruritusSkin and subcutaneous tissue disorders | 100/291 |
| VomitingGastrointestinal disorders | 90/291 |
| CoughRespiratory, thoracic and mediastinal disorders | 80/291 |
| NauseaGastrointestinal disorders | 78/291 |
| FeverGeneral disorders | 63/291 |
| EdemaGeneral disorders | 58/291 |
| Dry skinSkin and subcutaneous tissue disorders | 53/291 |
| Age, Continuous(years) | Participants With Refractory Bone Marrow Disease and High Risk of Recurrence |
|---|---|
| Median | 4 (0 to 29) |
| Sex: Female, Male(Participants) | Participants With Refractory Bone Marrow Disease and High Risk of Recurrence |
|---|---|
| Female | 112 |
| Male | 179 |
| Ethnicity (NIH/OMB)(Participants) | Participants With Refractory Bone Marrow Disease and High Risk of Recurrence |
|---|---|
| Hispanic or Latino | 21 |
| Not Hispanic or Latino | 270 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Participants With Refractory Bone Marrow Disease and High Risk of Recurrence |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 10 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 28 |
| White | 238 |
| More than one race | 0 |
| Unknown or Not Reported | 15 |
| Region of Enrollment(Participants) | Participants With Refractory Bone Marrow Disease and High Risk of Recurrence |
|---|---|
| United States | 291 |
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Memorial Sloan Kettering Cancer Center