Neuroblastoma
Conditions
Keywords
disseminated neuroblastoma, localized unresectable neuroblastoma, recurrent neuroblastoma, regional neuroblastoma, stage 4S neuroblastoma
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.
Interventions
BIOLOGICALanti-GD2 murine IgG3 monoclonal antibody 3F8
The total dosage of 3F8 per cycle is the same as in prior trials (100 mg/m2), administered at 20 mg/m2/day and infused over \ 1.5 hr or less (0.5 hr is customary), with analgesics and antihistamines used as needed for expected side-effects. 3F8 is started \ 1 hr after completion of GM-CSF administration. GM-CSF is dosed at 250 mcg/m2/day from day -5 to day +1 (Wednesday to Tuesday is customary) , and is 500 mcg/m2/day thereafter (i.e., on days +2 to +4; Wednesday to Friday), as in the predecessor protocol.18,74 Patients come off study if progressive disease occurs or if there is life-threatening grade 4 toxicity from 3F8; otherwise, patients will receive a minimum of 4 cycles of treatment and will continue treatment through 24 months. It is expected that patients will receive \ 10 cycles.
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy at Completion of Treatment | 3 years |
| Relapse-free Survival Every 3 Months | 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Compare Granulocyte Activation in Patients Treated With Short-term vs Prolonged Daily Exposure to Sargramostim (GM-CSF) After 4 Courses | 3 years |
| Simplify Treatment With Consequent Reduction in Cost | 3 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Refractory Bone Marrow Disease and High Risk of Recurrence Participants included have refractory bone marrow disease and high risk of recurrence of refractory bone marrow disease. All participants will receive anti-GD2 murine IgG3 monoclonal antibody 3F8. As per the study team, the data were not collected in the manner requested. As a result they cannot separate the patients into the respective protocol groups | 291 |
| Total | 291 |
Baseline characteristics
| Characteristic | Participants With Refractory Bone Marrow Disease and High Risk of Recurrence |
|---|---|
| Age, Continuous | 4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 270 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants |
| Race (NIH/OMB) White | 238 Participants |
| Region of Enrollment United States | 291 Participants |
| Sex: Female, Male Female | 112 Participants |
| Sex: Female, Male Male | 179 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 135 / 291 |
| other Total, other adverse events | 287 / 291 |
| serious Total, serious adverse events | 153 / 291 |
Outcome results
Primary
Efficacy at Completion of Treatment
Time frame: 3 years
Population: Data were not collected
Primary
Relapse-free Survival Every 3 Months
Time frame: 3 years
Population: Data were not collected
Secondary
Compare Granulocyte Activation in Patients Treated With Short-term vs Prolonged Daily Exposure to Sargramostim (GM-CSF) After 4 Courses
Time frame: 3 years
Population: Data were not collected
Secondary
Simplify Treatment With Consequent Reduction in Cost
Time frame: 3 years
Population: Data were not collected