Neuroblastoma
Conditions
Keywords
GM-CSF, MAB 3F8, RETINOIC ACID (CIS-9 & 13), 09-160
Brief summary
The purpose of this study is to 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 Acid
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 (20 mg/m2/day) for all cycles. The patients are in \> or = to 2nd CR/VGPR and at high risk for additional relapse. Real-time quantitative RT-PCR63-65 will be used to assess MRD in BM. 13-cis-retinoic acid is started after cycle 2.
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, MYCN-amplified stage 2 or stage 3 (any age), or MYCN-amplified stage 4S. * The patients are in \>2nd CR/VGPR, including no measurable MIBG-avid soft tissue tumor assessable for response. * 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 v34.0) 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 Impact of High-dose 3F8/GM-CSF on Relapse-free Survival | 2 years | in patients in second or greater complete or very good partial remission, but at high risk of additional relapse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apply Real-time Quantitative RT-PCR to Test the Hypothesis That the Minimal Residual Disease Content of Bone Marrow | 2 years | after the first treatments with 3F8/GMCSF has significant prognostic impact on relapse-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 Acid 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 (20 mg/m2/day) for all cycles. | 46 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Not Treated | 1 |
| Overall Study | Other | 4 |
| Overall Study | Other Complicating Disease | 3 |
| Overall Study | Progressive Disease | 26 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | 3F8/GM-CSF Immunotherapy Plus 13-Cis-Retinoic Acid |
|---|---|
| Age, Continuous | 6 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 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 | 1 Participants |
| Race (NIH/OMB) White | 41 Participants |
| Region of Enrollment United States | 46 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 46 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Assess the Impact of High-dose 3F8/GM-CSF on Relapse-free Survival
in patients in second or greater complete or very good partial remission, but at high risk of additional relapse.
Time frame: 2 years
Population: Data 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 relapse-free survival.
Time frame: 2 years
Population: Data 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 not collected