Safety and Efficacy of Sequential Treatment With a Combination of Rituximab, Fludarabine and Cyclophosphamide Followed by Zevalin (Rituximab and Y-Ibritumomab Tiuxetan) - A Phase I/II Study for Treatment of Patients With Relapsed Indolent and Transformed CD20-Positive B-Cell Non-Hodgkin's-Lymphoma Ineligible for High-Dose Chemo(Radio)Therapy Supported by Autologous Peripheral Blood Stem-Cells
- Determine the dose-limiting toxicity and maximum tolerated dose of rituximab and
yttrium Y 90 (^90Y) ibritumomab tiuxetan when administered with rituximab as
radioimmunotherapy after rituximab, fludarabine, and cyclophosphamide in patients with
relapsed indolent, mantle cell, or transformed CD20-positive B-cell non-Hodgkin's
- Determine the overall survival in patients treated with this regimen.
- Determine time to progression and event-free survival in patients treated with this
- Determine partial and complete response rates in patients treated with this regimen.
- Determine time to maximal response in patients treated with this regimen.
- Determine response duration in patients treated with this regimen.
- Determine the feasibility of additional antineoplastic treatment following disease
relapse after treatment with rituximab and ^90Y ibritumomab tiuxetan in these patients.
OUTLINE: This is a prospective, nonrandomized, multicenter, phase I dose-escalation study of
yttrium Y 90 (^90Y) ibritumomab tiuxetan followed by a phase II open-label study.
- Phase I:
- Chemoimmunotherapy: Patients receive rituximab IV on day 1 and fludarabine IV over
30 minutes and cyclophosphamide IV over 60 minutes on days 1-3. Treatment repeats
every 4 weeks for up to 3 courses in the absence of disease progression. Four
weeks after the first day of the last chemoimmunotherapy course, patients receive
1 dose of rituximab IV alone. Patients with disease progression are removed from
the study. Patients with stable disease proceed to radioimmunotherapy 8-12 weeks
after the first day of the last chemoimmunotherapy course.
- Radioimmunotherapy: Patients receive rituximab IV and an imaging dose of indium In
III ibritumomab tiuxetan IV over 10 minutes on day 1. Patients then undergo
imaging. If dosimetry is acceptable, patients receive rituximab IV and ^90Y
ibritumomab tiuxetan IV over 10 minutes on day 8.
Cohorts of 3-6 patients receive escalating doses of ^90Y ibritumomab tiuxetan 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.
- Phase II: Patients receive chemoimmunotherapy and radioimmunotherapy as in phase I, at
the MTD determined in phase I.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 2 years.
PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Christian Peschel, MD
Technische Universität München