- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01584388
Rituximab in IgG4-RD: A Phase 1-2 Trial
Rituximab (RTX) for IgG4-related Disease (IgG4-RD): a Prospective,Open-label Trial
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Patients will be included in the trial based on the following disease-specific criteria:
- Age 18 or older
Diagnosis of IgG4-RD, based upon either pathological criteria* (for those who have undergone biopsies) or clinical criteria.** The criteria for pathological and clinical diagnoses are specified below.
The subject can be either steroid-naive, in relapse, steroid dependent, or refractory to steroids. Subjects who are steroid dependent or refractory are eligible for enrollment if steroid dose has not been increased in the past 2 weeks, and their treating physician plans to withdraw steroids completely (by dose taper) within 8 weeks of starting rituximab.
Pathological diagnosis:
- Histopathologic features consisting of a lymphoplasmacytic infiltrate and storiform fibrosis within involved organs. Other histopathologic features consistent with IgG4-RD (e.g., obliterative phlebitis) may be present but are not required.
- Either an IgG4/IgG plasma cell ratio of > 50% within the affected organs or more than 10 IgG4-bearing plasma cells per high-power field.
All patients with pathologic diagnoses will have their specimens reviewed by pathology investigators.
**Clinical diagnosis:
• Organ involvement in a pattern consistent with IgG4-RD. This must include dysfunction of one of the following organs: pancreas (autoimmune pancreatitis); salivary glands (chronic sclerosing sialadenitis); lacrimal glands; orbital pseudotumor; kidneys; lungs; lymph nodes; meninges; aorta (including aortitis/periaortitis and/or retroperitoneal fibrosis); thyroid gland (Riedel's thyroiditis). If a patient is enrolled with a clinical diagnosis alone, the diagnosis must be accompanied by both an imaging finding compatible with IgG4-RD and a 1.5-fold elevation in the serum IgG4 concentration.
Exclusion Criteria:
Patients will be excluded from the study based on the following criteria:
Disease-Specific Concerns: Excessive fibrosis within organs, such that a disease response to rituximab would not be expected.
General Medical Concerns:
- Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment), or lactating.
- Inability to comply with study and/or follow-up procedures.
Rituximab-Specific Concerns:
- History of HIV.
- Presence of active infection.
- New York Heart Association Classification III or IV heart disease (See Appendix D).
- Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to randomization.
- Positive hepatitis B or C serology is considered a potential exclusion criterion. Hepatitis B screening should include hepatitis B antibody and surface antigen for a patient with no risk factors. For patients with risk factors or previous history of hepatitis B, add core antibodies and e-antigen.
- Allergies: History of severe allergic reactions to human or chimeric monoclonal antibodies or murine protein.
- Uncontrolled disease: They show evidence of other uncontrolled disease, including drug and alcohol abuse, which that could interfere with participation in the trial according to the protocol.
- History of anti-human anti-chimeric antibody formation.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rituximab
|
Rituximab 1000 mg IV times two doses, separated by approximately 15 days.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
IgG4-RD RI Score at Baseline and Six Months After Rituxan Treatment
Time Frame: 6 months
|
The IgG4-RD RI is then calculated by adding the individual organ scores.At each assessment, the physician enters a 0-4 score after the organ/site listed with: 0 = Normal or resolved
The Responder Index ranges from 0-60. |
6 months
|
Cumulative Glucocorticoid Use at Baseline and 6 Months
Time Frame: 6 months
|
Cumulative glucocorticoid therapy between baseline and 6 months.
|
6 months
|
No Disease Flares During Rituximab Treatment Phase
Time Frame: Month 6
|
Disease flare measured by responder Index score: At each assessment, the physician enters a 0-4 score after the organ/site listed with: 0 = Normal or resolved
|
Month 6
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Retreatment With Rituximab for Disease Relapse
Time Frame: 12 months
|
Number of subjects that relapsed during the course of the trial
|
12 months
|
Disease Response at 6 Months
Time Frame: 6 months
|
Decline of IgG4-RD Responder Index by at least two points for at least 6 months
|
6 months
|
Sustained Disease Response
Time Frame: 12 months
|
Decline of the IgG4-RD RI by at least two points and maintained for 12 months.
|
12 months
|
Complete Remission
Time Frame: 6 months
|
IgG4-RD RI (including serum IgG4) of 0 at six months
|
6 months
|
Complete Remission IgG-RD RI (Exclusive of Serum IgG4) of 0 at 6 Months.
Time Frame: 6 months
|
IgG-RD RI (exclusive of serum IgG4) of 0 at 6 months.
|
6 months
|
Complete Remission at Any Timepoint
Time Frame: 12 months
|
IgG4-RD RI = 0 at any point in the trial
|
12 months
|
Complete Remission (Any Timepoint), Exclusive of Serum IgG4
Time Frame: 12 months
|
IgG4-RD RI = 0 (exclusive of serum IgG4) at any point in the trial
|
12 months
|
Time to Disease Response
Time Frame: Mean days +/- standard deviation
|
Treatment phase up to 52 weeks (365 days)
|
Mean days +/- standard deviation
|
Time to Relapse
Time Frame: Days
|
Treatment phase up to 52 weeks (365 days)
|
Days
|
Time to Complete Remission
Time Frame: Days
|
Treatment phase up to 52 weeks (365 days)
|
Days
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: John H Stone, MD, MPH, Massachusetts General Hospital (Rheumatology Unit)
- Study Director: Arezou Khosroshahi, MD, Massachusetts General Hospital (Rheumatology Unit)
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Immune System Diseases
- Autoimmune Diseases
- Stomatognathic Diseases
- Mouth Diseases
- Pancreatic Diseases
- Salivary Gland Diseases
- Pancreatitis, Chronic
- Fibrosis
- Pancreatitis
- Retroperitoneal Fibrosis
- Autoimmune Pancreatitis
- Sialadenitis
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- 2011p002414
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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