Neuroblastoma
Conditions
Keywords
GM-CSF, MAB 3F8, RETINOIC ACID (CIS-9 & 13), 09-161
Brief summary
The purpose of this study is to see find out what effects, good and/or bad, the combination of 3F8 and GM-CSF has on the patient and the cancer.
Interventions
BIOLOGICAL3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic
This phase II, open-label, single arm trial assesses the anti-NB activity of high-dose 3F8 (80 mg/m2/day), which is used in cycles 1-2, with return to standard 3F8 dosage (20 mg/m2/day) in subsequent cycles.Clinical results will be compared to those in the predecessor trials which used only the standard 3F8 dosage. Starting with A(6), patients no longer receive high-dose 3F8 but receive only standard dose 3F8 (20mg/m2/day) for all cycles The patients have primary refractory BM disease. Protocol treatment is through 24 months. Real-time quantitative RT-PCR63-65 will be used to assess MRD in BM. 13-cis-retinoic acid is started no later than after cycle 4 (i.e., after response is scored), but sooner if CR is achieved after cycles 1, 2, or 3, or if early HAMA develops.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels. * High-risk NB as defined by risk-related treatment guidelines1 and the International NB Staging System,89 i.e., stage 4 with (any age) or without (\> or = to 18 months of age) MYCN amplification or MYCN-amplified stage 4S. * Patients have primary refractory disease limited to BM, i.e., high-risk NB (defined above) resistant to standard therapy, as evidenced by incomplete response in BM, but no measurable MIBG-avid soft tissue tumor assessable for response and no progressive disease. * Signed informed consent indicating awareness of the investigational nature of this program.
Exclusion criteria
* Creatinine \> 3.0 mg/dL * ALT, AST and Alkaline Phosphatase \> 5.0 times the upper limit of normal * Bilirubin \> 3.0 mg/dL * Patients with grade 3 or higher toxicities (using the CTCAE v 4.0) related to cardiac, neurological, pulmonary or gastrointestinal function as determined by physical exam. Patients must have normal blood pressure for age. * Progressive disease * History of allergy to mouse proteins. * Active life-threatening infection. * Human anti-mouse antibody (HAMA) titer \>1000 Elisa units/ml. * Inability to comply with protocol requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Activity of High-dose 3F8/GM-CSF | 2 years | against persistent neuroblastoma in bone marrow of patients who have no other evidence of disease by standard studies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apply Real-time Quantitative RT-PCR | 2 years | to test the hypothesis that the minimal residual disease content of bone marrow after the first treatments with 3F8/GMCSF has significant prognostic impact on progression-free survival. |
| Monitor Safety of the High-dose Antibody Treatment | 2 years | to assure no side-effects or noxious sequelae develop or emerge that were not seen in the prior phase I study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic This phase II study of the anti-GD2 murine IgG3 monoclonal antibody 3F8 combined with granulocyte-macrophage colony stimulating factor (GM-CSF) will assess response in of primary refractory neuroblastoma in bone marrow (i.e., incomplete response to standard treatment). | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic |
|---|---|
| Age, Categorical <=18 years | 31 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 2 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment Greece | 1 participants |
| Region of Enrollment Israel | 2 participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Assess the Activity of High-dose 3F8/GM-CSF
against persistent neuroblastoma in bone marrow of patients who have no other evidence of disease by standard studies.
Time frame: 2 years
Population: Data were not collected
Secondary
Apply Real-time Quantitative RT-PCR
to test the hypothesis that the minimal residual disease content of bone marrow after the first treatments with 3F8/GMCSF has significant prognostic impact on progression-free survival.
Time frame: 2 years
Population: Data were not collected
Secondary
Monitor Safety of the High-dose Antibody Treatment
to assure no side-effects or noxious sequelae develop or emerge that were not seen in the prior phase I study.
Time frame: 2 years
Population: Data were not collected