Primary Refractory Neuroblastoma
Conditions
Keywords
Neuroblastoma, 3F8, Primary refractory
Brief summary
This is a multicenter, randomized, controlled, open-label study. Patients meeting inclusion/exclusion criteria will be randomized (1:1) to receive two cycles of MAb-3F8 plus GM-CSF or RA plus GM-CSF. Patients who do not respond to their assigned treatment after two cycles may cross-over to receive the alternate treatment. Disease response and safety will be assessed in all patients after cycle 2 and after cycle 4.
Interventions
BIOLOGICALMAb-3F8
BIOLOGICALSubcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
BIOLOGICAL13-cis-Retinoic Acid
Sponsors
United Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Months to 13 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of stage 4 neuroblastoma diagnosed in accordance with the International Neuroblastoma Staging System: either (a) histologic confirmation which may involve immunohistochemical, ultrastructural, and/or cytogenetic studies, or (b) elevated urinary catecholamines plus tumor cells/clumps in the bone marrow. * Have evaluable disease or biopsy-proven stable disease in BM by histology or MIBG scan with MIBG-positive disease confined to the bone or bone marrow, plus urine catecholamine results, documented \>3 weeks after conventional chemotherapy or \>6 weeks after stem-cell transplantation. CT, MRI, or bone scan (if necessary) can be done at 2-3 weeks after conventional chemotherapy confirming that the chemotherapy, radiotherapy, and ABMT are not realistic curative options. * Be between 18 months to 13 years old at diagnosis. * Have recovered to grade 2 or better toxicities since their prior therapy. * Must, if female of childbearing potential, be willing to use two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at screening and monthly thereafter through the first four cycles of treatment. * Have a performance score of at least 60 from Lansky Play Performance Scale if aged up to 16 years or at least 60 from Karnofsky Scale if aged more than 16 years. * Have voluntarily agreed to participate.
Exclusion criteria
* Have measurable disease ≥ 1 cm assessed by CT or MRI. * Have progressive disease (any new lesion; increase of any measurable lesion by \>25%; or previous negative marrow positive for tumor). * Have disease detectable in CNS (confirmed by CT or MRI of the brain at screening or within 8 weeks of randomization). * Be receiving alternative therapy for the treatment of neuroblastoma, e.g. radiotherapy or chemotherapy within 3 weeks of randomization. * Require additional therapy (such as radiotherapy) during the first two treatment cycles. * Have detectable human anti-mouse antibody titers at screening. * Have received prior anti-GD2 investigational therapies. * Have a history of allergies to mouse proteins. * Have an active infection requiring IV infusion of antibiotics. * Be currently receiving long-term chronic treatment with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), or systemic corticosteroids.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the proportion of patients achieving a complete bone marrow response measured by an absence of histological evidence of bone marrow disease and by MIBG scan after two cycles of treatment. | two years |
Secondary
| Measure | Time frame |
|---|---|
| A comparison in treatment arms for disease response as measured by CT/MRI scan and urine catecholamines, MIBG extent of disease scores, disease response in cross-over patients. | two years |
Countries
United States
Outcome results
None listed