Neuroblastoma
Conditions
Keywords
Anti-GD2 3F8 Monoclonal Antibody, oral isotretinoin, GM-CSF, Sargramostim, 13-260
Brief summary
The purpose of this study is to be able to supply an experimental combination of drugs called 3F8 and GM-CSF (also called sargramostim) to patients with high-risk neuroblastoma who may benefit from treatment.
Detailed description
This treatment uses 3F8/GM-CSF and isotretinoin for: Group 1 patients are in 1st CR/VGPR; Group 2 patients are in a ≥2nd CR/VGPR; and Group 3 patients have primary refractory NB in BM. All patients will receive 3F8/GM-CSF through 24 months. Road Map/Schema for Group 1 (1st CR/VGPR) and Group 2 (≥2nd CR/VGPR) patients: Cycle 1 3F8 (iv) + GM-CSF subcutaneous (sc) (1 wk) 2-4-wk interval Cycle 2 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval\* - oral isotretinoin x14 days Cycle 3 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 4 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on Cycle 5 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) Cycle 6 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval Cycle 7 3F8 (iv) + GM-CSF (sc) (1 wk) Continue with 6-8-wk intervals through 24 months from 1st dose of 3F8. \* assessment of BM status by standard histology Road Map/Schema for Group 3 patients (BM positive): The break between end of a cycle of 3F8/GM-CSF and start of next cycle is approximately 2-to-4-weeks through 4 cycles after achievement of CR in BM; subsequent breaks are \ 6-8 weeks. Please see roadmap below for a patient achieving CR in BM after cycle 1. Cycle 1 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval\* - BM negative Cycle 2 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval\* - oral isotretinoin x14 days Cycle 3 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 4 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 5 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days Cycle 6 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) Cycle 7 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval Continue with 6-8-wk intervals through 24 months from 1st dose of 3F8. \* assessment of BM response by standard histology
Interventions
BIOLOGICALAnti-GD2 3F8 Monoclonal Antibody
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Diagnosis of NB as defined by international criteria,62 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels. * High-risk NB, as defined by risk-related treatment guidelines and the International NB Staging System, i.e., stage 4 with (any age) or without (\>18 months) MYCNamplification, 63 or MYCN-amplified NB other than stage 1.64,65 * Patients are in CR/VGPR or have primary refractory NB in BM - i.e., NB resistant to standard therapy, as evidenced by persistence of NB in BM by histology or MIBG scan, but all other findings in scans show VGPR. * Children and adults are eligible. * Signed informed consent indicating awareness of the scheduling and side effects, as well as testing requirements, of this program.
Exclusion criteria
* Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity \> or = to grade 3, except for grade 3 hematologic toxicity. * Progressive disease (PD) * History of allergy to mouse proteins. * Active life-threatening infection. * Human anti-mouse antibody (HAMA) titer \>1000 Elisa units/ml. * Pregnant women * Inability to comply with protocol requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Therapeutic Response | 2 years | Disease status is defined by the International Neuroblastoma Response Criteria - Complete response/remission (CR): NED; Partial response/remission: \>50% decrease in all disease parameters, exceptbone scan unchanged or improved; no more than 1 positive bone marrow site; Stable disease: \<50% decrease in all tumor markers; Progressive disease (PD): new lesion, or \>25 % increase in any disease marker. |
| Complete Remission | 2 years | Disease status is defined by the International Neuroblastoma Response Criteria - Complete response/remission (CR): NED; Partial response/remission: \>50% decrease in all disease parameters, exceptbone scan unchanged or improved; no more than 1 positive bone marrow site; Stable disease: \<50% decrease in all tumor markers; Progressive disease (PD): new lesion, or \>25 % increase in any disease marker. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neuroblastoma This is a single-arm, open label, open access study to provide the anti-GD2 murine IgG3 MoAb 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with high-risk neuroblastoma (NB). This immunotherapy has shown efficacy against minimal residual disease (MRD) in such patients.
Anti-GD2 3F8 Monoclonal Antibody
GM-CSF (granulocyte-macrophage colony-stimulating factor)
oral isotretinoin | 69 |
| Total | 69 |
Baseline characteristics
| Characteristic | Neuroblastoma |
|---|---|
| Age, Continuous | 4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 6 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 | 7 Participants |
| Race (NIH/OMB) White | 52 Participants |
| Region of Enrollment United States | 69 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 69 |
| other Total, other adverse events | 69 / 69 |
| serious Total, serious adverse events | 26 / 69 |
Outcome results
Primary
Complete Remission
Disease status is defined by the International Neuroblastoma Response Criteria - Complete response/remission (CR): NED; Partial response/remission: \>50% decrease in all disease parameters, exceptbone scan unchanged or improved; no more than 1 positive bone marrow site; Stable disease: \<50% decrease in all tumor markers; Progressive disease (PD): new lesion, or \>25 % increase in any disease marker.
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Neuroblastoma | Complete Remission | Stable Disease | 6 Participants |
| Neuroblastoma | Complete Remission | Progression of Disease | 19 Participants |
| Neuroblastoma | Complete Remission | No Evidence of Disease | 40 Participants |
| Neuroblastoma | Complete Remission | Complete Response | 3 Participants |
| Neuroblastoma | Complete Remission | Partial Response | 1 Participants |
Primary
Therapeutic Response
Disease status is defined by the International Neuroblastoma Response Criteria - Complete response/remission (CR): NED; Partial response/remission: \>50% decrease in all disease parameters, exceptbone scan unchanged or improved; no more than 1 positive bone marrow site; Stable disease: \<50% decrease in all tumor markers; Progressive disease (PD): new lesion, or \>25 % increase in any disease marker.
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Neuroblastoma | Therapeutic Response | Partial Response | 1 Participants |
| Neuroblastoma | Therapeutic Response | No Evidence of Disease | 40 Participants |
| Neuroblastoma | Therapeutic Response | Complete Response | 3 Participants |
| Neuroblastoma | Therapeutic Response | Stable Disease | 6 Participants |
| Neuroblastoma | Therapeutic Response | Progression of Disease | 19 Participants |