NeuroblastomaPhase 2NCT00072358
Monoclonal Antibody 3F8 and Sargramostim in Treating Patients With Neuroblastoma
A Phase 2 study testing anti-GD2 murine IgG3 monoclonal antibody 3F8 in people with Neuroblastoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- anti-GD2 murine IgG3 monoclonal antibody 3F8
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 291 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2003to 15 Jan 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of neuroblastoma by histopathology OR bone marrow metastases and high urine catecholamine levels
- Disease must meet risk-related treatment guidelines and any of the following International Neuroblastoma Staging System stages:
- Stage 4 with (any age) OR without (> 18 months of age of age) MYCN amplification
- MYCN-amplified other than stage 1
- No evidence of disease (i.e., in complete response/remission or very good partial response/remission) OR disease resistant to standard therapy (i.e., incomplete response in bone marrow)
- No progressive disease or MIBG-avid soft tissue tumor
PATIENT CHARACTERISTICS:
- No existing renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3
- No human anti-mouse antibody (HAMA) titer greater than 1,000 Elisa units/mL
- No history of allergy to mouse proteins
- No active life-threatening infection
- Not pregnant
- Negative pregnancy test
PRIOR CONCURRENT THERAPY:
- Not specified
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase II Study of Anti-GD2 3F8 Antibody and GM-CSF for High-Risk Neuroblastoma
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.
Read the detailed description
OBJECTIVES:
- Determine the efficacy of sargramostim (GM-CSF) in enhancing monoclonal antibody 3F8-mediated ablation in patients with high-risk neuroblastoma.
- Determine the prognostic impact of minimal residual bone marrow disease on relapse-free survival of patients treated with this regimen.
- Compare the effects of short-term (2-hour intravenous) vs prolonged (subcutaneous release) daily GM-CSF on granulocyte activation, in order to establish the optimal route for tumor-cell kill in these patients.
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.
- Conditions
- Neuroblastoma
- Being tested
- anti-GD2 murine IgG3 monoclonal antibody 3F8
- Keywords
- disseminated neuroblastoma, localized unresectable neuroblastoma, recurrent neuroblastoma, regional neuroblastoma, stage 4S neuroblastoma
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-GD2 murine IgG3 monoclonal antibody 3F8Biological
Also called 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
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.
anti-GD2 murine IgG3 monoclonal antibody 3F8Biological
Also called 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
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.
| Study group | Role | What they receive |
|---|---|---|
| patients have refractory bone marrow disease | Experimental | 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. Receives: Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8 |
| patients have no evidence of disease | Experimental | 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. Receives: Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy at Completion of Treatment
Measured: 3 years
Relapse-free Survival Every 3 Months
Measured: 3 years
Secondary outcomes (2)
Compare Granulocyte Activation in Patients Treated With Short-term vs Prolonged Daily Exposure to Sargramostim (GM-CSF) After 4 Courses
Measured: 3 years
Simplify Treatment With Consequent Reduction in Cost
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2003 (estimated)
- Study startJul 2003
- Primary completion15 Jan 2021
- Study completion15 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 291 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Brian H. Kushner, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00072358
- Sponsor's protocol ID
- 03-077
- Other IDs
- MSKCC-03077
- Status last verified
- Apr 2022
- First submitted
- 4 Nov 2003
- Last updated
- 16 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Kushner BH, White C, Mauguen A, Cardenas FI, Basu EM, Wei W, Kramer K, Modak S. Naxitamab with novel scheduling and stepped-up dosing of GM-CSF plus vaccine, but no myeloablative therapy for patients with high-risk neuroblastoma in first complete remission. Int J Cancer. 2026 Jun 1;158(11):2928-2935. doi: 10.1002/ijc.70329. Epub 2026 Jan 10.
PubMed 41518133Kushner BH, Modak S, Basu EM, Roberts SS, Kramer K, Cheung NK. Posterior reversible encephalopathy syndrome in neuroblastoma patients receiving anti-GD2 3F8 monoclonal antibody. Cancer. 2013 Aug 1;119(15):2789-95. doi: 10.1002/cncr.28137. Epub 2013 Apr 30.
PubMed 23633099Cheung IY, Hsu K, Cheung NK. Activation of peripheral-blood granulocytes is strongly correlated with patient outcome after immunotherapy with anti-GD2 monoclonal antibody and granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2012 Feb 1;30(4):426-32. doi: 10.1200/JCO.2011.37.6236. Epub 2011 Dec 27.
PubMed 22203761
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Anti-GD2 3F8 Antibody and GM-CSF for High-Risk Neuroblastoma
- ClinicalTrials.gov ID
- NCT00072358
- Acronym / sponsor ID
- 03-077
- Conditions
- Neuroblastoma
- Keywords
- disseminated neuroblastoma, localized unresectable neuroblastoma, recurrent neuroblastoma, regional neuroblastoma, stage 4S neuroblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 291 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2003
- Primary completion
- 15 Jan 2021 (actual)
- Study completion
- 15 Jan 2021 (actual)
- First posted
- 6 Nov 2003 (estimated)
- Results
- Posted 16 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
- Determine the efficacy of sargramostim (GM-CSF) in enhancing monoclonal antibody 3F8-mediated ablation in patients with high-risk neuroblastoma.
- Determine the prognostic impact of minimal residual bone marrow disease on relapse-free survival of patients treated with this regimen.
- Compare the effects of short-term (2-hour intravenous) vs prolonged (subcutaneous release) daily GM-CSF on granulocyte activation, in order to establish the optimal route for tumor-cell kill in these patients.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patients have refractory bone marrow disease | Experimental | Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8This 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. |
| patients have no evidence of disease | Experimental | Biological: anti-GD2 murine IgG3 monoclonal antibody 3F8This 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-GD2 murine IgG3 monoclonal antibody 3F8Also: 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 afterThe 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. | Biological | patients have refractory bone marrow disease |
| anti-GD2 murine IgG3 monoclonal antibody 3F8Also: 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 theThe 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. | Biological | patients have no evidence of disease |
Primary outcome
Efficacy at Completion of Treatment
Time frame: 3 years
Relapse-free Survival Every 3 Months
Time frame: 3 years
2 secondary outcomes
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41518133Kushner BH, White C, Mauguen A, Cardenas FI, Basu EM, Wei W, Kramer K, Modak S. Naxitamab with novel scheduling and stepped-up dosing of GM-CSF plus vaccine, but no myeloablative therapy for patients with high-risk neuroblastoma in first complete remission. Int J Cancer. 2026 Jun 1;158(11):2928-2935. doi: 10.1002/ijc.70329. Epub 2026 Jan 10.
- Derived from this study: PubMed 23633099Kushner BH, Modak S, Basu EM, Roberts SS, Kramer K, Cheung NK. Posterior reversible encephalopathy syndrome in neuroblastoma patients receiving anti-GD2 3F8 monoclonal antibody. Cancer. 2013 Aug 1;119(15):2789-95. doi: 10.1002/cncr.28137. Epub 2013 Apr 30.
- Derived from this study: PubMed 22203761Cheung IY, Hsu K, Cheung NK. Activation of peripheral-blood granulocytes is strongly correlated with patient outcome after immunotherapy with anti-GD2 monoclonal antibody and granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2012 Feb 1;30(4):426-32. doi: 10.1200/JCO.2011.37.6236. Epub 2011 Dec 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian H. Kushner, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing anti-GD2 murine IgG3 monoclonal antibody 3F8 in people with Neuroblastoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy at Completion of Treatment (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00072358, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2022.