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).

Study Overview

• Status: Completed
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: recombinant human interleukin 21 and rituximab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of adverse events through 1 month after completing treatment	During treatment and through 1 month after completing treatment
Incidence and grade of clinical laboratory abnormalities through 1 month after treatment	During treatment and through 1 month after completing treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease response by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas 2 weeks after completion of the first treatment cycle	Two and four weeks after completion of the first and second cycles, respectively
Immunogenicity by incidence of anti-rIL-21 antibodies up to 1 month after treatment	During treatment and up to 1 month after completing treatment

Collaborators and Investigators

• Sponsor: ZymoGenetics
• Investigators: Study Director: Muriel Siadak, PA-C, ZymoGenetics

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: June 30, 2006
• First Submitted That Met QC Criteria: June 30, 2006
• First Posted (Estimate): July 4, 2006

Study Record Updates

• Last Update Posted (Estimate): September 5, 2008
• Last Update Submitted That Met QC Criteria: September 4, 2008
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Keywords: Immunotherapy; Lymphoma, Non-Hodgkin; interleukin-21; rituximab
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 494E03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No