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

Primary Purpose

Neuroblastoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
monoclonal antibody 3F8
sargramostim
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring recurrent neuroblastoma, stage 4S neuroblastoma, disseminated neuroblastoma, localized unresectable neuroblastoma, regional neuroblastoma

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

3F8 and GM-CSF

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose of monoclonal antibody 3F8
Anti-neuroblastoma effects of monoclonal antibody 3F8 and sargramostim (GM-CSF)

Secondary Outcome Measures

Full Information

First Posted
March 20, 2007
Last Updated
October 14, 2013
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00450307
Brief Title
Monoclonal Antibody 3F8 and GM-CSF in Treating Young Patients With High-Risk, Refractory or Relapsed Neuroblastoma
Official Title
3F8 Antibody Dose Escalation Plus Granulocyte-Macrophage Colony-Stimulating Factor in High-Risk Neuroblastoma: A Phase I Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
recurrent neuroblastoma, stage 4S neuroblastoma, disseminated neuroblastoma, localized unresectable neuroblastoma, regional neuroblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
3F8 and GM-CSF
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
monoclonal antibody 3F8
Intervention Type
Biological
Intervention Name(s)
sargramostim
Primary Outcome Measure Information:
Title
Maximum tolerated dose of monoclonal antibody 3F8
Time Frame
2 years
Title
Anti-neuroblastoma effects of monoclonal antibody 3F8 and sargramostim (GM-CSF)
Time Frame
2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian H. Kushner, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21343563
Citation
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.
Results Reference
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Monoclonal Antibody 3F8 and GM-CSF in Treating Young Patients With High-Risk, Refractory or Relapsed Neuroblastoma

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