A PHASE I STUDY OF CHIMERIC HUMAN/MURINE ANTI-GD2 MONOCLONAL ANTIBODY (ch14.18) WITH GM-CSF AND INTERLEUKIN-2 (IL-2) IN CHILDREN WITH NEUROBLASTOMA IMMEDIATELY POST AUTOLOGOUS BMT OR PBSC RESCUE
I. Determine the maximum tolerated dose of monoclonal antibody (MOAB) ch14.18 when combined
with sargramostim (GM-CSF) and interleukin-2 (IL-2) after autologous bone marrow or
peripheral blood stem cell rescue in children with neuroblastoma.
II. Determine the toxic effects of this regimen in these patients. III. Determine the
pharmacokinetics, including antibody level, antibody-binding activity, and presence of human
anti-chimeric antibodies, of this regimen in these patients.
IV. Determine the activity of IL-2 and MOAB ch14.18 against tumor cells in terms of response
using standard clinical measurements such as bone marrow immunocytology in these patients.
V. Determine the extent of coating of tumor cells (bone marrow metastases) by MOAB ch14.18
in these patients.
VI. Determine the feasibility of isotretinoin administered between courses beginning after
course 2 in these patients.
OUTLINE: This is a multicenter, dose-escalation study of monoclonal antibody (MOAB).
Patients receive MOAB IV over 5 hours on days 7-10 during courses 2 and 4 and on days 3-6
during courses 1, 3, and 5; sargramostim (GM-CSF) IV over 2 hours or subcutaneously daily on
days 0-13 during courses 1, 3, and 5; interleukin-2 IV continuously on days 0-3 and 7-10
during courses 2 and 4; and oral isotretinoin twice daily on days 14-27 during courses 2 and
4 and on days 10-23 during courses 3 and 5. Treatment repeats every 24-32 days for 5 courses
in the absence of unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of MOAB until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. A minimum of 6 additional patients are treated
at the MTD.
Patients are followed every other week for 2 months and then every 3 months for 6 months.
PROJECTED ACCRUAL: Approximately 6-16 patients will be accrued for this study within 1 year.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of monoclonal antibody (MOAB) ch14.18 when combined with sargramostim and IL-2 after autologous bone marrow or peripheral blood stem cell rescue in children with neuroblastoma
Children's Oncology Group
United States: Institutional Review Board
|Children's Oncology Group||Arcadia, California 91006-3776|