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

United Therapeutics

Status and phase: Terminated; Phase 2

Conditions: Primary Refractory Neuroblastoma

Treatments: Biological: Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF); Biological: MAb-3F8; Biological: 13-cis-Retinoic Acid

Study type: Interventional

Funder types: Industry

Identifiers

NCT00969722

3F8-NB-201

Details and patient eligibility

About

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.

Enrollment: 1 patient

Sex: All

Ages: 18 months to 13 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1 participants in 2 patient groups

ARM I

Experimental group

Description:

Intravenous MAb-3F8 plus Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)

Treatment:

Biological: Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)

Biological: MAb-3F8

ARM II

Active Comparator group

Description:

Oral 13-cis-Retinoic Acid (RA) plus Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)

Treatment:

Biological: 13-cis-Retinoic Acid

Biological: Subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)