Clinical trial NCT00072358: Monoclonal Antibody 3F8 and Sargramostim in Treating Patients With Neuroblastoma
Official title: Phase II Study of Anti-GD2 3F8 Antibody and GM-CSF for High-Risk Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: disseminated neuroblastoma
localized unresectable neuroblastoma
recurrent neuroblastoma
regional neuroblastoma
stage 4S neuroblastoma
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-11-06
Enrollment: 291
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy at Completion of Treatment
timeFrame: 3 years
measure: Relapse-free Survival Every 3 Months
timeFrame: 3 years
Secondary outcomes:
measure: Compare Granulocyte Activation in Patients Treated With Short-term vs Prolonged Daily Exposure to Sargramostim (GM-CSF) After 4 Courses
timeFrame: 3 years
measure: Simplify Treatment With Consequent Reduction in Cost
timeFrame: 3 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Brian H. Kushner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kushner 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.
citation: Cheung 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.