Study Evaluating Rapid Infusion Rituximab in Patients With Autoimmune Diseases

Multiple Sclerosis Clinical Trial

Official title:

Study Evaluating Rapid Infusion Rituximab in Patients With Autoimmune Diseases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02040116
• Other study ID #: IRB00022197
• Status: Completed
• Phase: Phase 4
• Start date: February 2013
• Est. completion date: August 2014

Study information

• Verified date: August 2018
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Autoimmune Diseases
• Multiple Sclerosis

Intervention

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.

Locations

Country	Name	City	State
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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