Multiple Sclerosis
Conditions
Keywords
Rapid Infusion Rituximab
Brief 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.
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.
Interventions
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.
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Infusion Related Reactions With Rapid Infusion Will be Reported | 14 Days | 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. |
| Grade of Infusion Related Reactions With Rapid Infusion Will be Reported | 14 Days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Chair Time With Rapid Infusion Will be Reported | 14 Days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 20 hours
Rapid Infusion Rituximab: 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. | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Rituximab Infusion |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 40 years |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
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.
Time frame: 14 Days
Population: Due to their being no reactions, the Grade of reactions for Standard infusion will and can not be reported, as the lowest grade requires there to be a reaction.
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.
Time frame: 14 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Number of Reactions for Standard Infusion | Incidence of Infusion Related Reactions With Rapid Infusion Will be Reported | 0 infusion reactions |
| Number of Reactions for Rapid Infusion | Incidence of Infusion Related Reactions With Rapid Infusion Will be Reported | 0 infusion reactions |
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.
Time frame: 14 Days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Number of Reactions for Standard Infusion | Change in Chair Time With Rapid Infusion Will be Reported | -10 Hours |