NCT00397800

Rituximab, Fludarabine, Cyclophosphamide, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed B-Cell Non-Hodgkin's Lymphoma

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

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Technical University of Munich · Academic / Other
• Sex: All
• Age: 50 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving rituximab and chemotherapy together with yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of yttrium Y 90 ibritumomab tiuxetan when given together with rituximab, fludarabine, and cyclophosphamide and to see how well they work in treating patients with relapsed B-cell non-Hodgkin's lymphoma.

Detailed description

OBJECTIVES: Primary * 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 lymphoma. Secondary * Determine the overall survival in patients treated with this regimen. * Determine time to progression and event-free survival in patients treated with this regimen. * 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.

Conditions

• Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	rituximab
DRUG	cyclophosphamide
DRUG	fludarabine phosphate
RADIATION	yttrium Y 90 ibritumomab tiuxetan

Timeline

• Start date: 2005-06-01
• Primary completion: 2008-05-01
• Completion: 2013-05-01
• First posted: 2006-11-10
• Last updated: 2012-08-28

Locations

12 sites across 1 country: Germany