AzTrials
AzTrials

Retroperitoneal FibrosisPhase 1/2NCT01584388

Rituximab in IgG4-RD: A Phase 1-2 Trial

A Phase 1/2 study testing Rituximab in people with Retroperitoneal Fibrosis and Autoimmune Pancreatitis, run by Massachusetts General Hospital.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
No sites listed yet
Study dates
Apr 2012to Jan 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 10Show fewer
  • 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.

Who cannot join

  • 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:
Show all 15Show fewer
  • 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.

About this study

Official title: Rituximab (RTX) for IgG4-related Disease (IgG4-RD): a Prospective,Open-label Trial

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

Read the 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.

Being tested
Rituximab
Keywords
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
Medical subject headings
Retroperitoneal Fibrosis, Autoimmune Pancreatitis, Sialadenitis, Orbital Pseudotumor, Lymphadenopathy, Meningitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    Also called Rituxan

    Rituximab 1000 mg IV times two doses, separated by approximately 15 days.

Study groups in NCT01584388
Study groupRoleWhat they receive
RituximabExperimentalNot described
Receives: Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. IgG4-RD RI Score at Baseline and Six Months After Rituxan Treatment

    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

    1. = Improved but still present
    2. = Persistent (still active; unchanged from previous visit)
    3. = New or recurrent disease activity while patient is off treatment
    4. = Worsened or new disease despite treatment Definitions Organ/Site score: The overall level of IgG4-RD activity within a specific organ system Symptomatic: Is the disease manifestation in a particular organ system symptomatic? (Y = yes; N = no) Urgent disease: Disease that requires treatment immediately to prevent serious organ dysfunction (Y = yes; N = no) (Presence of urgent disease within an organ leads to DOUBLING of that organ system score) Damage: Organ dysfunction that has occurred as a result of IgG4-RD and is considered permanent (Y = yes; N = no)

    The Responder Index ranges from 0-60.

    Measured: 6 months

  2. Cumulative Glucocorticoid Use at Baseline and 6 Months

    Cumulative glucocorticoid therapy between baseline and 6 months.

    Measured: 6 months

  3. No Disease Flares During Rituximab Treatment Phase

    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

    1. = Improved but still present
    2. = Persistent (still active; unchanged from previous visit)
    3. = New or recurrent disease activity while patient is off treatment
    4. = Worsened or new disease despite treatment Definitions Organ/Site score: The overall level of IgG4-RD activity within a specific organ system Symptomatic: Is the disease manifestation in a particular organ system symptomatic? (Y = yes; N = no) Urgent disease: Disease that requires treatment immediately to prevent serious organ dysfunction (Y = yes; N = no) (Presence of urgent disease within an organ leads to DOUBLING of that organ system score) Damage: Organ dysfunction that has occurred as a result of IgG4-RD and is considered permanent (Y = yes; N = no)

    Measured: Month 6

Secondary outcomes (10)

  1. Retreatment With Rituximab for Disease Relapse

    Number of subjects that relapsed during the course of the trial

    Measured: 12 months

  2. Disease Response at 6 Months

    Decline of IgG4-RD Responder Index by at least two points for at least 6 months

    Measured: 6 months

  3. Sustained Disease Response

    Decline of the IgG4-RD RI by at least two points and maintained for 12 months.

    Measured: 12 months

  4. Complete Remission

    IgG4-RD RI (including serum IgG4) of 0 at six months

    Measured: 6 months

  5. Complete Remission IgG-RD RI (Exclusive of Serum IgG4) of 0 at 6 Months.

    IgG-RD RI (exclusive of serum IgG4) of 0 at 6 months.

    Measured: 6 months

  6. Complete Remission at Any Timepoint

    IgG4-RD RI = 0 at any point in the trial

    Measured: 12 months

  7. Complete Remission (Any Timepoint), Exclusive of Serum IgG4

    IgG4-RD RI = 0 (exclusive of serum IgG4) at any point in the trial

    Measured: 12 months

  8. Time to Disease Response

    Treatment phase up to 52 weeks (365 days)

    Measured: Mean days +/- standard deviation

  9. Time to Relapse

    Treatment phase up to 52 weeks (365 days)

    Measured: Days

  10. Time to Complete Remission

    Treatment phase up to 52 weeks (365 days)

    Measured: Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionJan 2014
  4. Study completionJan 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01584388
Sponsor's protocol ID
2011p002414
Status last verified
May 2017
First submitted
22 Apr 2012
Last updated
2 Jul 2017
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Carruthers MN, Topazian MD, Khosroshahi A, Witzig TE, Wallace ZS, Hart PA, Deshpande V, Smyrk TC, Chari S, Stone JH. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis. 2015 Jun;74(6):1171-7. doi: 10.1136/annrheumdis-2014-206605. Epub 2015 Feb 9.

    PubMed 25667206

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Rituximab in people with Retroperitoneal Fibrosis and Autoimmune Pancreatitis, run by Massachusetts General Hospital.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

IgG4-RD RI Score at Baseline and Six Months After Rituxan Treatment (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01584388, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in