Study Evaluating Rapid Infusion Rituximab in Patients With Autoimmune Diseases

The purpose of this study is to evaluate the impact of rapid infusion rituximab on the incidence of infusion-related reactions in patients with Autoimmune Diseases.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Rituximab Infusion

Detailed Description

Background Rituximab is a human/murine monoclonal antibody targeted at the CD20 antigen (cluster of differentiation antigen 20) on B-lymphocytes. The CD20 antigen is expressed in over 90% of B-cell non-Hodgkin's lymphomas. B cells are also believed to play a role in the pathogenesis of other oncologic and non-oncologic disorders. Targeting B cells appears to have a role in decreasing autoimmune and inflammatory processes, as well as antibody production in many autoimmune diseases. Rituximab is approved for the treatment of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA) in combination with methotrexate, wegener's granulomatosis, and microscopic polyangiitis in combination with glucocorticoids. Although rituximab is not approved for multiple sclerosis, myasthenia gravis, or other autoimmune diseases, it is commonly used later in the treatment course for patients that are not responding to other treatment options. Rituximab's main limitation is the occurrence of infusion-related reactions (IRR). These reactions can include fever, chills, rash, respiratory compromise, and a variety of other symptoms, including death. The incidence of IRR is known to vary depending on the rituximab indication. The incidence of IRR with the first infusion of rituximab is approximately 77% with NHL, 27% with RA, and 12% with wegener's granulomatosis and microscopic polyangiitis. The incidence of IRR decreases with subsequent infusions of rituximab to approximately 5-10%. According to the National Cancer Institute, there are 5 grades of IRR. In general, grade 1 reactions are classified as asymptomatic or only mild symptoms that do not require intervention. Grade 2 reactions are classified as moderate with minimal, local, or noninvasive interventions required. Grade 3 reactions are classified as severe and medically significant, but not immediately life-threatening. These reactions require hospitalization or prolongation of a current hospitalization. Grade 4 reactions are classified as life-threatening with urgent interventions required. Grade 5 reactions are classified as death related to an adverse drug event. The incidence of IRR is a chief concern for patients, nurses, and other healthcare providers.

The package labeling recommends the administration of a standard infusion of rituximab for all patients initiating rituximab therapy to minimize IRR. If this infusion is tolerated then subsequent infusions may be titrated up to a faster rate to decrease infusion time. Based on the manufacturer's package insert, rituximab is infused at a rate of 50 mg/hr and can be increased every 30 minutes by 50 mg/hr (maximum rate of 400 mg/hr). If a grade 3 or 4 IRR does not occur, subsequent infusions are given at a rate of 100 mg/hr and can be increased every 30 minutes by 100 mg/hr (maximum rate of 400 mg/hr). The average infusion time is estimated to be 4-6 hours for the first infusion, and 3-4 hours for subsequent infusions. Rituximab is typically given in cycles and the timing will vary depending on the indication.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Autoimmune patient at Wake Forest Baptist Health that is eligible for rituximab therapy
• Tolerate the standard infusion rituximab with ≤ grade 2 hypersensitivity reaction
• Consent to participate in the rapid infusion study
• Age ≥ 18 years ≤ 80 years

Exclusion Criteria:

• Tolerate the standard infusion rituximab with ≥ grade 3 hypersensitivity reaction
• Neurocognitive impairment (i.e. dementia, Alzheimers, et al)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: rituximab infusion; Every patient is getting the same therapy of rituximab. If day 1 is tolerated at standard infusion then day 14 and beyond will be given as rapid infusion over 90 minutes	Drug: Rituximab Infusion; Participants will receive their first infusion of rituximab at the standard infusion rate provided in the manufacturer labeling. If they tolerate this infusion with a grade 2 of less infusion-related reaction, the next infusion will be administered as a 90 minute rapid infusion.; Other Names: Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Infusion Related Reactions With Rapid Infusion Will be Reported	Patients are given therapy on day 1 and if infusion is tolerated with < grade 2 reaction based on the CTCAE v4 then then will proceed to rapid infusion on day 14 which is given over 90 minutes. The number of infusion reaction is measured for all patients and in all infusions given.	14 Days
Grade of Infusion Related Reactions With Rapid Infusion Will be Reported	Patients are given therapy on day 1 and if infusion is tolerated with < grade 2 reaction based on the CTCAE v4 then then will proceed to rapid infusion on day 14 which is given over 90 minutes. The grade of infusion reaction is measured for all patients and in all infusions given. According to the National Cancer Institute, there are 5 grades of IRR. In general, grade 1 reactions are classified as asymptomatic or only mild symptoms that do not require intervention. Grade 2 reactions are classified as moderate with minimal, local, or noninvasive interventions required. Grade 3 reactions are classified as severe and medically significant, but not immediately life-threatening. These reactions require hospitalization or prolongation of a current hospitalization. Grade 4 reactions are classified as life-threatening with urgent interventions required. Grade 5 reactions are classified as death related to an adverse drug event.	14 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Chair Time With Rapid Infusion Will be Reported	The amount of time spent administering the rituximab will be compared to the time from the first infusion to the second infusion. The change was calculated from two time points as the value at the later time point minus the value at the earlier time point.	14 Days

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: LeAnne D Kennedy, PharmD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: January 14, 2014
• First Submitted That Met QC Criteria: January 17, 2014
• First Posted (Estimate): January 20, 2014

Study Record Updates

• Last Update Posted (Actual): September 7, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Rapid Infusion Rituximab
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Autoimmune Diseases; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: IRB00022197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No