Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00072592
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2003-11-04
Brief Title:
An Open Label Pilot Study Examining the Use of Rituximab in Patients With Wegeners Granulomatosis Who Have Experienced Disease Relapse on Standard Therapies
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
An Open Label Pilot Study Examining the Use of Rituximab in Patients With Wegeners Granulomatosis Who Have Experienced Disease Relapse on Standard Therapies
Status:
COMPLETED
Status Verified Date:
2005-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the use of rituximab in patients with Wegeners granulomatosis WG who have experienced a relapse of the disease through standard therapies Rituximab is an antibody directed against the human protein called CD20 found on the surface of normal and abnormal B lymphocytes Rituximab decreases the number of B lymphocytes This study will examine the safety of rituximab in WG and rituximabs ability to reduce the level of circulating antineutrophil cytoplasmic antibodies ANCA which are antibodies that react to substances found in white blood cells ANCA have been found to be strongly associated with WG The study will also explore whether rituximab can reduce the occurrence of disease relapse WG is a disease marked by inflammation of blood vessels It can involve many different parts of the body including the sinuses lungs kidneys brain nerves eyes intestinal tract skin joint heart and others Before the use of cytotoxic drug therapy WG was almost always fatal if untreated with a mortality rate of 93 within 2 years
Patients 18 to 75 years of age who have a history of at least one relapse of the disease despite standard treatments who have had active WG within the previous 12 months and are in remission who are receiving either methotrexate or azathioprine for remission maintenance and who have circulating ANCA may be eligible for this study
A minimum of 22 visits to the clinic will be required to complete the entire study Patients will undergo a comprehensive medical evaluation with laboratory studies and x-rays There may also be consultations and possible biopsies of affected organs only if medically indicated for diagnosis and treatment of the disease In the 4-week period that patients will receive rituximab infusions the methotrexate or azathioprine will be continued at the same dosage unless there are side effects that requite the medication to be temporarily stopped or the dosage reduced Patients will receive four doses of rituximab at 375 mg per meter squared of body surface area once a week It will be infused into a vein through an intravenous catheter For the first dose patients will be admitted as inpatients for at least 24 hours for monitoring during the infusion and for any reactions associated with it The second third and fourth rituximab infusions may be given either on an inpatient or outpatient basis to be decided on how the patient tolerates the first infusion
Following the four infusions there will be blood tests to monitor the safety of the medication and the status of the disease to be done at home every week for 4 weeks Results will be sent to the researchers by fax Patients will be asked to return to the clinic 1 month after the fourth infusion and every 1 to 3 months afterward If there are no side effects or a relapse of the disease the methotrexate or azathioprine will be continued for 2 years past remission If by then the disease then remains in remission the dose of either medication will be gradually decreased and eventually stopped The usual schedule is to reduce methotrexate by 25 mg per month and to reduce azathioprine by 25 mg per month If at that point there are no signs of active disease the patients illness will be considered to be in continued remission and no further treatment will be necessary If relapse does occur treatment would be different than previously In most cases treatment would involve prednisone and cyclophosphamide or methotrexate If the ANCA finding is negative after rituximab treatment and again becomes positive and there is evidence of a return of B lymphocytes patients may receive a second course of four rituximab infusions
Patients 18 to 75 years of age who have a history of at least one relapse of the disease despite standard treatments who have had active WG within the previous 12 months and are in remission who are receiving either methotrexate or azathioprine for remission maintenance and who have circulating ANCA may be eligible for this study
A minimum of 22 visits to the clinic will be required to complete the entire study Patients will undergo a comprehensive medical evaluation with laboratory studies and x-rays There may also be consultations and possible biopsies of affected organs only if medically indicated for diagnosis and treatment of the disease In the 4-week period that patients will receive rituximab infusions the methotrexate or azathioprine will be continued at the same dosage unless there are side effects that requite the medication to be temporarily stopped or the dosage reduced Patients will receive four doses of rituximab at 375 mg per meter squared of body surface area once a week It will be infused into a vein through an intravenous catheter For the first dose patients will be admitted as inpatients for at least 24 hours for monitoring during the infusion and for any reactions associated with it The second third and fourth rituximab infusions may be given either on an inpatient or outpatient basis to be decided on how the patient tolerates the first infusion
Following the four infusions there will be blood tests to monitor the safety of the medication and the status of the disease to be done at home every week for 4 weeks Results will be sent to the researchers by fax Patients will be asked to return to the clinic 1 month after the fourth infusion and every 1 to 3 months afterward If there are no side effects or a relapse of the disease the methotrexate or azathioprine will be continued for 2 years past remission If by then the disease then remains in remission the dose of either medication will be gradually decreased and eventually stopped The usual schedule is to reduce methotrexate by 25 mg per month and to reduce azathioprine by 25 mg per month If at that point there are no signs of active disease the patients illness will be considered to be in continued remission and no further treatment will be necessary If relapse does occur treatment would be different than previously In most cases treatment would involve prednisone and cyclophosphamide or methotrexate If the ANCA finding is negative after rituximab treatment and again becomes positive and there is evidence of a return of B lymphocytes patients may receive a second course of four rituximab infusions
Detailed Description:
This pilot study will seek to investigate the use of rituximab in patients with Wegeners granulomatosis who have experienced disease relapse through standard therapies Rituximab is a chimeric monoclonal antibody directed against CD20 which induces B cell death and results in rapid and sustained depletion of circulating and tissue-based B cells The objectives of this protocol will be to establish the safety of rituximab in Wegeners granulomatosis to examine the ability of rituximab to reduce the level of circulating antineutrophil cytoplasmic antibodies ANCA and to preliminarily explore whether rituximab is able to prevent disease relapse This prospective standardized open label trial will enroll 10 patients who have a well-documented history of disease relapse while receiving immunosuppressive therapy given according to published regimens and who are ANCA positive after remission induction Patients will be enrolled once they have achieved remission from a recent relapse and are receiving either methotrexate or azathioprine for remission maintenance All patients will receive rituximab 375 mgM2 once a week for 4 weeks During and following the rituximab treatment period patients will remain on their remission maintenance agent of methotrexate or azathioprine Patients who are enrolled while on prednisone will continue to taper the dosage to discontinuation as medically permitted Following the 4 weekly infusions of rituximab patients will be followed prospectively for evidence of effective B cell depletion features of drug toxicity level of circulating ANCA and clinical disease status Patients whose ANCA levels become undetectable following the infusion of rituximab may be retreated with a second 4 week course of rituximab should their ANCA titer become positive greater than or equal to 140 and there has been a return of B cells in the peripheral blood Methotrexate or azathioprine will be continued for two years past remission after which time this will be tapered and discontinued Patients will continue to be monitored for two years off all immunosuppressive therapy or if a disease relapse should occur for a minimum of 12 months after the last rituximab infusion
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-I-0022 | None | None | None |