Rituximab in IgG4-related Disease: A Phase 1-2 Trial

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
John H. Stone, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01584388
First received: April 22, 2012
Last updated: October 18, 2013
Last verified: October 2013
  Purpose

The primary objective of this study is to evaluate the safety and effectiveness of rituximab in IgG4-RD.


Condition Intervention Phase
Retroperitoneal Fibrosis
Autoimmune Pancreatitis
Sialadenitis
Pseudotumor
Drug: Rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rituximab in IgG4-Related Disease: A Phase 1-2 Trial

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Primary (Disease Response) [ Time Frame: Six months ] [ Designated as safety issue: No ]

    Disease Response at six months is the primary endpoint in this trial. The ability to maintain disease remission off glucocorticoids is an important clinical measure in this disease.

    Disease Response - Disease Response is defined at 6 months as:

    • Improvement of > 2 points in the IgG4-RD RI over baseline
    • No glucocorticoid or other immunosuppressive drug use between months 4 and 6
    • No disease flares, as assessed by the IgG4-RD Responder Index.


Estimated Enrollment: 30
Study Start Date: April 2012
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab Drug: Rituximab
Rituximab 1000 mg IV times two doses, separated by approximately 15 days.
Other Name: Rituxan

Detailed Description:

This two-center trial will enroll at total of 30 patients with IgG4-RD. The two participating sites are the Massachusetts General Hospital (Boston, MA) and the Mayo Clinic (Rochester, MN). All patients will receive rituximab 1 gram intravenously times two doses, separated by approximately 15 days. The primary efficacy outcome - disease remission and successful completion of the glucocorticoid taper - will be assessed at six months. Patients will be followed on the protocol for an additional six months after measurement of the primary outcome.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01584388

Sponsors and Collaborators
Massachusetts General Hospital
Genentech, Inc.
Investigators
Study Chair: John H Stone, MD, MPH Massachusetts General Hospital (Rheumatology Unit)
Study Director: Arezou Khosroshahi, MD Massachusetts General Hospital (Rheumatology Unit)
  More Information

No publications provided

Responsible Party: John H. Stone, MD, Director, Clinical Rheumatology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01584388     History of Changes
Other Study ID Numbers: 2011p002414
Study First Received: April 22, 2012
Last Updated: October 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Type 1 autoimmune pancreatitis
IgG4-related sclerosing cholangitis
Chronic sclerosing sialadenitis
Lacrimal glands
Orbital pseudotumor
IgG4-related tubulointerstitial nephritis
Lymphadenopathy
Pachymeningitis
Aorta
Peri-aortitis
Retroperitoneal fibrosis
Riedel's thyroiditis

Additional relevant MeSH terms:
Pancreatitis
Fibrosis
Retroperitoneal Fibrosis
Sialadenitis
Digestive System Diseases
Mouth Diseases
Pancreatic Diseases
Pathologic Processes
Salivary Gland Diseases
Stomatognathic Diseases
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014