Trial Information

Ibritumomab Tiuxetan and High-Dose Melphalan as Conditioning Regimen Before Autologous Stem Cell Transplantation for Elderly Patients With Lymphoma in Relapse or Resistant to Chemotherapy. A Multicenter Phase I Trial

OBJECTIVES:

- Determine the maximum tolerated dose of high-dose melphalan when given together with
yttrium Y 90 ibritumomab tiuxetan and rituximab as a conditioning regimen followed by
vinorelbine ditartrate- and filgrastim (G-CSF)-mobilized autologous stem cell
transplantation in elderly patients with relapsed or refractory CD20-positive
non-Hodgkin's lymphoma.

- Evaluate the feasibility and safety of this regimen in these patients.

- Determine the feasibility of stem cell mobilization with vinorelbine ditartrate in
patients treated with this regimen.

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

- Stem cell harvest and mobilization: Patients receive vinorelbine ditartrate IV on day
-36 and filgrastim (G-CSF) subcutaneously (SC) twice daily on days -33 to -29. Patients
undergo peripheral blood stem cell harvest on days -29 to -26.

- Radioimmunotherapy: Patients receive rituximab IV. Within 4 hours after completion of
rituximab, patients receive indium In 111 ibritumomab tiuxetan (imaging dose) IV over
10 minutes on day -25. Patients undergo assessment of biodistribution, imaging, and
dosimetry on days -25, -22, and optionally on day -20. Patients with acceptable
biodistribution of indium In 111 ibritumomab tiuxetan receive rituximab IV followed by
yttrium Y 90 ibritumomab tiuxetan (therapeutic dose) IV over 10 minutes on day -18.

- High-dose chemotherapy: Patients receive high-dose melphalan IV on day -1. Cohorts of
3-6 patients receive escalating doses of high-dose melphalan until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity.

- Autologous stem cell transplantation (ASCT): Patients undergo ASCT on day 0. Patients
receive G-CSF SC beginning on day 5 and continuing until blood counts recover.

After completion of study treatment, patients are followed for 100 days.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.