Clinical trial NCT00969722: A Study of MAb-3F8 Plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus 13-cis-Retinoic Acid (RA) Plus GM-CSF in Primary Refractory Neuroblastoma Patients
Official title: A Randomized Study of Monoclonal Antibody 3F8 Plus Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Compared to 13-cis-Retinoic Acid Plus GM-CSF in High Risk Stage 4, Primary Refractory Neuroblastoma Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Refractory Neuroblastoma
Keywords: Neuroblastoma
3F8
Primary refractory
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2009-09-01
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: two years
Secondary outcomes:
measure: 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.
timeFrame: two years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: San Diego
country: United States
facility: Rady Children's Hospital of San Diego
state: California
city: Washington
country: United States
facility: Georgetown Medical Center
state: District of Columbia
city: St. Petersburg
country: United States
facility: All Children's Hospital in Florida
state: Florida
city: New Orleans
country: United States
facility: LSU Health Sciences Center; Children's Hospital
state: Louisiana
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Childrens Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Cancer Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Dallas
country: United States
facility: US Oncology
state: Texas
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Burlington
country: United States
facility: Vermont Cancer Center
state: Vermont
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Peter E. Zage, M.D.
role: PRINCIPAL_INVESTIGATOR
References: