Neuroblastoma
Conditions
Keywords
MAB 3F8, RETINOIC ACID (CIS-9 & 13), Bone Marrow, 09-159
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. Antibodies are made by the body to attack tumors and to fight infections. 3F8 is the name of one kind of antibody. It is made by mice, and it can attack neuroblastoma in people. 3F8 has been used safely in many patients, and it has killed cancer cells in some patients. One way it can kill cancer cells is by causing the patient's own white blood cells to attack the cancer. Granulocytes are one kind of white blood cell. GM-CSF increases the number of granulocytes in people, and it makes the granulocytes better able to kill the cancer cells.
Interventions
DRUG3F8 and 13-cis-retinoic acid
3F8 is dosed at 80 mg/m2/day (cycles 1-2) or 20 mg/m2/day (cycles 3 and beyond) and infused iv over 30-90 minutes. 13-cis-retinoic acid is dosed at 160 mg/m2/day, divided into two doses, x14 days. If a dose is missed, it can be made up at the end of the cycle. It is not taken on same days as 3F8. \*High-dose 3F8 will be administered only for patients enrolled on protocol from A(0) to A(7). Starting with A(8), patients receive standard dose (20mg/m2/day) during cycles 1 and 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 (≥18 months of age) MYCN amplification, MYCN-amplified stage 2 or stage 3 (any age), or MYCN-amplified stage 4S. * The patients are in first CR/VGPR after conventional therapy. They have 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 v3.0) 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 | 2 years | on relapse-free survival in patients in first complete or very good partial remission, but at high risk of relapse. |
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 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 and 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(8), patients no longer receive high dose 3F8 but receive only standard dose 3F8 (20mg/m2/day) for all cycles.
3F8 and 13-cis-retinoic acid: 3F8 is dosed at 80 mg/m2/day (cycles 1-2) or 20 mg/m2/day (cycles 3 and beyond) and infused iv over 30-90 minutes. 13-cis-retinoic acid is dosed at 160 mg/m2/day, divided into two doses, x14 days. If a dose is missed, it can be made up at the end of the cycle. It is not taken on same days as 3F8. \*High-dose 3F8 will be administered only for patients enrolled on protocol from A(0) to A(7). Starting with A(8), patients receive standard dose (20mg/m2/day) during cycles 1 and 2. | 39 |
| Total | 39 |
Baseline characteristics
| Characteristic | 3F8 and 13-cis-retinoic Acid |
|---|---|
| Age, Categorical <=18 years | 39 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 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 | 5 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment Colombia | 1 Participants |
| Region of Enrollment Greece | 1 Participants |
| Region of Enrollment India | 1 Participants |
| Region of Enrollment Singapore | 1 Participants |
| Region of Enrollment Spain | 2 Participants |
| Region of Enrollment United States | 33 Participants |
| Sex: Female, Male Female | 17 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 Impact of High-dose 3F8/GM-CSF
on relapse-free survival in patients in first complete or very good partial remission, but at high risk of relapse.
Time frame: 2 years
Population: No data were 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: No data were 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: No data were collected