NANT 99-02: Modulation of Intensive Melphalan (L-PAM) by Buthionine Sulfoximine (BSO) with Autologous Stem Cell Support for Recurrent High-Risk Neuroblastoma (A Phase I Study)

Why are we doing this research?

1. Determine the maximum tolerated dose of melphalan when combined with buthionine sulfoximine and followed by autologous bone marrow or peripheral blood stem cell support in children with recurrent high-risk neuroblastoma.

2. Assess the toxic effects of this regimen in these patients.

3. Determine the pharmacokinetics of this regimen in these patients.

4. Determine the response rate of patients treated with this regimen.


  • Cancer - Neuroblastoma


  • Female
  • Male

What will happen in the study?

This is a multicenter, dose-escalation study of melphalan.

Patients receive buthionine sulfoximine IV as a bolus over 30 minutes followed by a 72-hour continuous infusion beginning on day -4; melphalan IV over 15 minutes on days -3 and -2; autologous peripheral blood stem cells or bone marrow IV over 15-30 minutes on day 0; and filgrastim (G-CSF) subcutaneously or IV once daily beginning on day 0 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of melphalan 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.

Patients are followed at 84 days and then 2 months later if there is a complete and/or partial response. Patients who continue therapy on other protocols are followed before starting the new therapy. All patients are followed for life for any delayed toxic effects to protocol therapy and secondary malignancies.