Study of Recombinant Interleukin 21 in Combination With Rituxan for Non-Hodgkin's Lymphoma

Phase 1, Open-Label, Dose-Escalation Study to Assess the Safety and Pharmacokinetics of Recombinant Interleukin 21 (rIL-21) Administered in Combination With Rituxan (Rituximab) in Subjects With B-Cell Non Hodgkin's Lymphoma

The purpose of the study is to evaluate whether recombinant IL-21 used in combination with rituximab is safe for patients with non-Hodgkin's lymphoma (NHL).

This is a Phase 1 open-label dose-escalation study of rituximab + rIL-21 combination therapy, administered once weekly for 4 weeks following an initial treatment with one dose of rituximab alone to patients with B-cell non-Hodgkin's lymphoma (NHL) who have failed prior therapy(ies). A standard dose of rituximab will be used. Increasing doses of rIL-21 will be studied sequentially in different groups of patients, starting with 30 μg/kg.

Before starting treatment with rituximab + rIL-21, patients will be treated with one dose of rituximab alone to look for rituximab infusion-related symptoms (such as fever, chills, and rigors). Patients who have severe infusion-related side effects after the first dose of rituximab will not go on to receive IL-21. Those who do not have unacceptable rituximab-related side effects will receive intravenous rIL-21 at least 60 minutes after completing the rituximab infusion at the rest of the weekly dosing visits. Patients will be evaluated for safety over the course of the study. Disease evaluation (tumor restaging) will be performed 2 weeks following completion of the first 4-week treatment cycle. Patients with stable disease or better at this evaluation may go on to receive a second 4-week treatment cycle of rituximab + rIL-21. Patients may be in the study for 2 to 4 months.

Inclusion Criteria:

• Diagnosis of CD20+ B-cell NHL
• Disease measurable by computed tomography (CT) scan
• Has failed at least one prior systemic therapy for NHL
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hepatic and renal function
• Adequate bone marrow function

Exclusion Criteria:

• Presence of acute infection or other significant systemic illness
• White blood cell (WBC) count > 50,000/mm3 in peripheral blood
• Central nervous system involvement by malignancy
• Previous allogenic transplant or autotransplant within 6 months of enrollment
• Other current malignancy or known history of cancer within 5 years
• Received systemic corticosteroids, chemotherapy, immunotherapy, biologic therapy, antibody therapy (e.g., rituximab), radiation therapy, and/or investigational agent(s) within 1 month of enrollment