Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma

NCT01757626 | Active Not Recruiting Phase 1

• 1 other identifier: 12-230
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if an antibody called Humanized 3F8 (Hu3F8) combined with granulocyte- macrophage colony stimulating factor (GM-CSF) is safe for treating neuroblastoma.

Conditions

Neuroblastoma

Keywords

Bone Marrow; Hu3F8; GM-CSF; 12-230

Outcome Measures

Primary Outcomes (2)

• maximum tolerated dosage

  hu3F8 when combined with GM-CSF. DLT is defined after 1 cycle. Seventeen dosage levels of hu3F8 will be tested with three to six patients at each dosage level.

  1 year

• assess the toxicity

  of the humanized anti GD2 antibody hu3F8 when combined with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in patients with high risk neuroblastoma. All observed adverse events, regardless of treatment group or suspected causal relationship to study drug will be recorded. Adverse events will be identified and graded using the Common Toxicity Criteria Version 4.0

  1 year

Secondary Outcomes (3)

• pharmacokinetics of hu3F8

  1 year

• assess activity of hu3F8 plus GM-CSF against HR-NB

  2 years

• quantitate the response of marrow NB

  1 year

Study Arms (2)

Hu3F8 with GM-CSF

EXPERIMENTAL

The phase I single arm trial assesses escalating doses of iv hu3F8 (days 1, 3, 5) in the presence of sc GM-CSF (day -4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. The expansion phase II single arm trial assesses the anti-NB activity of hu3F8+GM-CSF.in 3 groups of patients: Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123I-MIBG scan. Group 2 patients are in ≥2nd CR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123I-MIBG scan. Ph II: Groups 1 \& 3 pts can continue to get cycles every 1-2 months for up to 24 months from study enrollment or until they receive 5 cycles after a major response (CR or PR) is achieved.

Biological: Hu3F8 With GM-CSF

expansion phase II single arm trial

EXPERIMENTAL

Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123\^I-MIBG scan. Group 2 patients are in \>2nd CR/VGPR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123\^I-MIBG scan. GM-CSF can be omitted if patients have a history of an allergy to GM-CSF or develop an allergic reaction to GM-CSF after initiating therapy while on the protocol.

Biological: Hu3F8 With GM-CSF

Interventions

Hu3F8 With GM-CSF BIOLOGICAL

Ph I: 1 cycle consists of treatment with hu3F8 for 3 days (day 1, 3 \& 5). GM-CSF starts 5 days in advance of each hu3F8 cycle at 250 mcg/m\^2/day (day -4 to day 0), \& at 500 mcg/m\^2/day x 5 days (day 1 to day 5). Hu3F8 cycles are 5 days. Ph II pts may receive treatment on a modified schedule of 3 doses of IV hu3F8 over a maximum of 10 days, as needed. With modified schedules of hu3F8, GM-CSF will be administered at 250 mcg/m2/day x5 days before the 1st dose of hu3F8, as with the standard schedule, but then GM-CSF at 500 mcg/m2/day will be administered on day of the 1st dose of hu3F8, on the day before and on the day of the 2nd dose of hu3F8, and on the day before and on the day of the 3rd dose of hu3F8. Cycles are repeated at 2-4 week intervals between 1st days of hu3F8, through 4 cycles. Pts who complete 4 cycles of treatment w/o complications or disease progression have the option of continuing treatment for up to 24 months from their 1st dose of hu3F8.

Hu3F8 with GM-CSF

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels.
• Patients must have high-risk NB (including MYCNamplified stage 2/3/4/4S of any age and MYCN-nonamplified stage 4 in patients greater than 18 months of age) AND:
• Phase I: Patients must have refractory or relapsed NB, resistant to standard therapy\*.
• \*For NB, standard therapy includes intensive induction chemotherapy, followed by a variety of consolidation or salvage therapies, depending on response.
• Phase II: Patients must have primary or secondary refractory disease in BM, defined as morphologic evidence of NB in BM and/or abnormal 123I-MIBG uptake in osteomedullary sites, OR patients patients in ≥ 2nd CR patients are in ≥2nd CR
• Patients must be older than 1 year of age.
• Prior treatment with murine and humanized 3F8 is allowed. Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have a negative HAHA antibody titer. Human anti-mouse antibody (HAMA) positivity is allowed.
• White blood cell count ≥1000/ul (phase I only)
• Absolute neutrophil count ≥500/ul (phase I only)
• Absolute lymphocyte count ≥500/ul (phase I only)
• Platelet count ≥25,000/ul (phase I only)
• No chemotherapy or immunotherapy for a minimum of three weeks prior to start of hu3F8
• Women of child-bearing potential must be willing to practice an effective method of birth control while on treatment
• Signed informed consent indicating awareness of the investigational nature of this program.

You may not qualify if:

• Existing major organ dysfunction \> grade 2, with the exception of hearing loss and hematologic toxicity (defined as suppression of all subtypes of WBCs, RBCs, and platelets).
• Active life-threatening infection.
• Pregnant women or women who are breast-feeding.
• Inability to comply with protocol requirements, including PK studies and genetic studies (phase I only)
• History of allergy to mouse proteins.
• Positive human anti-hu3F8 antibody (HAHA) titer

Sponsors & Collaborators

• Y-mAbs Therapeutics: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (4)

• Kushner BH, Modak S, White C, Basu EM, Roberts SS, Mauguen A, Cheung NV. A phase II trial of naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in second or later complete remission. Int J Cancer. 2026 Feb 11. doi: 10.1002/ijc.70374. Online ahead of print.

  PMID: 41670398 DERIVED

• Kushner BH, Modak S, Mauguen A, Basu EM, Roberts SS, Cheung NV. Naxitamab plus stepped-up dosing of granulocyte-macrophage colony-stimulating factor for primary refractory high-risk neuroblastoma: results of a phase I/II trial. J Hematol Oncol. 2025 Nov 26;18(1):114. doi: 10.1186/s13045-025-01770-7.

  PMID: 41299684 DERIVED

• Kushner BH, Cheung IY, Modak S, Basu EM, Roberts SS, Cheung NK. Humanized 3F8 Anti-GD2 Monoclonal Antibody Dosing With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Resistant Neuroblastoma: A Phase 1 Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):1729-1735. doi: 10.1001/jamaoncol.2018.4005.

  PMID: 30326045 DERIVED

• Cheung IY, Kushner BH, Modak S, Basu EM, Roberts SS, Cheung NV. Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus GM-CSF: Impact of body weight, immunogenicity and anti-GD2 response on pharmacokinetics and survival. Oncoimmunology. 2017 Jul 31;6(11):e1358331. doi: 10.1080/2162402X.2017.1358331. eCollection 2017.

  PMID: 29147617 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Neuroblastoma

Interventions

naxitamab; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Brian Kushner, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2012
• First Posted: December 31, 2012
• Study Start: December 1, 2012
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

US (1)