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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00450307
First received: March 20, 2007
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Biological: monoclonal antibody 3F8
Biological: sargramostim
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 3F8 Antibody Dose Escalation Plus Granulocyte-Macrophage Colony-Stimulating Factor in High-Risk Neuroblastoma: A Phase I Trial

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose of monoclonal antibody 3F8 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Anti-neuroblastoma effects of monoclonal antibody 3F8 and sargramostim (GM-CSF) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: June 2005
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 3F8 and GM-CSF
One cycle has 5 days of 3F8 treatment. Each day, patients receive GM-CSF subcutaneously ~1.5 hr before the start 3F8 infusion. To limit side-effects, patients receive analgesics, antihistamines, and a small dose (IV, over ~5 minutes) of heat-modified 3F8. Cycles can be repeated after a 2-4 week interval, up to a total of two cycles.
Biological: monoclonal antibody 3F8 Biological: sargramostim

Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00450307

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Brian H. Kushner, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00450307     History of Changes
Other Study ID Numbers: 05-015, MSKCC-05015
Study First Received: March 20, 2007
Last Updated: October 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
recurrent neuroblastoma
stage 4S neuroblastoma
disseminated neuroblastoma
localized unresectable neuroblastoma
regional neuroblastoma

Additional relevant MeSH terms:
Neuroblastoma
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
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 29, 2014