Monoclonal Antibody 3F8 and GM-CSF in Treating Young Patients With High-Risk, Refractory or Relapsed Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

3F8 Antibody Dose Escalation Plus Granulocyte-Macrophage Colony-Stimulating Factor in High-Risk Neuroblastoma: A Phase I Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00450307
• Other study ID #: 05-015
• Secondary ID: MSKCC-05015
• Status: Completed
• Phase: Phase 1
• First received: March 20, 2007
• Last updated: October 14, 2013
• Start date: June 2005
• Est. completion date: April 2013

Study information

• Verified date: October 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies, such as 3F8, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving monoclonal antibody therapy together with GM-CSF may be an effective treatment for neuroblastoma.

PURPOSE: This phase I trial is studying the side effects and best dose of monoclonal antibody 3F8 when given together with GM-CSF in treating young patients with high-risk, refractory or relapsed neuroblastoma.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of monoclonal antibody 3F8 when administered with sargramostim (GM-CSF) in young patients with high-risk, refractory or relapsed neuroblastoma.

• Assess anti-neuroblastoma effects of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of monoclonal antibody 3F8.

Patients receive sargramostim (GM-CSF) subcutaneously once daily on days -5 to 11 and monoclonal antibody 3F8 IV over 30 minutes on days 0-4 and 7-11. Treatment repeats every 4-6 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of monoclonal antibody 3F8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• Patients must have a diagnosis of NB as defined by international criteria,45 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels.

• Patients must have refractory or relapsed high-risk NB (including MYCNamplified stage 3/4/4S and MYCN-nonamplified stage 4 >18 months old) resistant to standard therapy.

• Prior treatment with 3F8 is allowed.

• Age <21 years.

• Signed informed consent indicating awareness of the investigational nature of this program.

Exclusion Criteria:

• Existing major organ dysfunction should be grade 2 or less, with the exception of myelosuppression (neutrophil count >500/ul and platelet count >10,000/ul are acceptable), alopecia, hearing loss. Patient cannot be taking antihypertensive medication.

• History of allergy to mouse proteins.

• Active life-threatening infection.

• Human anti-mouse antibody (HAMA) titer >1000 ELISA units/ml.

• Prior treatment with 3F8 is NOT an exclusion criterion.

• Inability to comply with protocol requirements.

• Pregnant women are excluded for fear of danger to the fetus. Therefore negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is used during the study period.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Biological:
• monoclonal antibody 3F8

• sargramostim

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kushner BH, Kramer K, Modak S, Cheung NK. Successful multifold dose escalation of anti-GD2 monoclonal antibody 3F8 in patients with neuroblastoma: a phase I study. J Clin Oncol. 2011 Mar 20;29(9):1168-74. doi: 10.1200/JCO.2010.28.3317. Epub 2011 Feb 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of monoclonal antibody 3F8		2 years	Yes
Primary	Anti-neuroblastoma effects of monoclonal antibody 3F8 and sargramostim (GM-CSF)		2 years	No