Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE2
43 participants
INTERVENTIONAL
2015-07-09
2019-02-08
Brief Summary
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Detailed Description
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The drugs used in treatment of lupus nephritis often do not cure the disease and can cause serious side effects, including lowering the immune system too much. When the immune system is too low, a person is at a higher risk of getting infections. Therefore, research into new treatments with fewer serious side effects is needed for lupus nephritis.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Rituximab/Cyclophosphamide (RC)
Prednisone taper to 10 mg/day by week 12 and continue prednisone 10 mg/day to week 96.
Rituximab
Rituximab 1000mg intravenously (IV) at week 0 and week 2
Cyclophosphamide
Cyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2.
Prednisone
* Week 0 and Week 2: Prednisone (40 mg/day; taper to 10 mg/day by week 12)
* Continue prednisone 10 mg/day to week 96
Methylprednisolone
Week 0 and Week 2:
Solumedrol (100 mg) IV
Diphenhydramine
Diphenhydramine (50 mg, or equivalent dose of similar antihistamine) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
Acetaminophen
Acetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
Rituximab/Cyclophosphamide/Belimumab (RCB)
1. Belimumab (10 mg/kg IV) at weeks 4, 6, 8, and every 4 weeks to week 48.
2. Prednisone taper to 10 mg/day by week 12, and continue prednisone 10 mg/day to week 96.
Rituximab
Rituximab 1000mg intravenously (IV) at week 0 and week 2.
Cyclophosphamide
Cyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2.
Prednisone
* Week 0 and Week 2: Prednisone (40 mg/day; taper to 10 mg/day by week 12)
* Continue prednisone 10 mg/day to week 96
Methylprednisolone
Week 0 and Week 2: Solumedrol (100 mg) IV
Diphenhydramine
Diphenhydramine (50 mg, or equivalent dose of similar antihistamine) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
Acetaminophen
Acetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
Belimumab
The RCB Group will receive IV belimumab 10mg/kg at weeks 4, 6, 8, and then every 4 weeks through week 48
Interventions
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Rituximab
Rituximab 1000mg intravenously (IV) at week 0 and week 2
Cyclophosphamide
Cyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2.
Prednisone
* Week 0 and Week 2: Prednisone (40 mg/day; taper to 10 mg/day by week 12)
* Continue prednisone 10 mg/day to week 96
Methylprednisolone
Week 0 and Week 2:
Solumedrol (100 mg) IV
Diphenhydramine
Diphenhydramine (50 mg, or equivalent dose of similar antihistamine) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
Acetaminophen
Acetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
Rituximab
Rituximab 1000mg intravenously (IV) at week 0 and week 2.
Cyclophosphamide
Cyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2.
Prednisone
* Week 0 and Week 2: Prednisone (40 mg/day; taper to 10 mg/day by week 12)
* Continue prednisone 10 mg/day to week 96
Methylprednisolone
Week 0 and Week 2: Solumedrol (100 mg) IV
Diphenhydramine
Diphenhydramine (50 mg, or equivalent dose of similar antihistamine) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
Acetaminophen
Acetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
Belimumab
The RCB Group will receive IV belimumab 10mg/kg at weeks 4, 6, 8, and then every 4 weeks through week 48
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Positive antinuclear antibody (ANA) or positive anti-ds DNA test results at visit -1 or any time within 14 days before visit -1.
3. Active proliferative lupus nephritis, as defined by either of the following:
* Kidney biopsy documentation within the last 3 months of International Society of Nephrology/Renal Pathology Society (ISN/RPS) proliferative nephritis: Class III, Class IV, or Class V in combination with Class III or IV.
* Active urinary sediment and kidney biopsy documentation within the last 12 months of ISN/RPS proliferative nephritis: Class III, Class IV, or Class V in combination with Class III or IV. Active urinary sediment is defined as any one of the following:
* \>5 RBC/hpf in the absence of menses and infection;
* \>5 White blood cell per high powered field (WBC/hpf) in the absence of infection; or
* Cellular casts limited to RBC or WBC casts.
4. Urine protein-to-creatinine ratio (UPCR) \>1 at study entry based on a 24-hour collection.
5. Ability to provide informed consent.
Exclusion Criteria
2. Neutropenia (absolute neutrophil count \<1500/mm\^3).
3. Thrombocytopenia (platelets \<50,000/mm\^3).
4. Moderately severe anemia (Hgb \< mg/dL).
5. Moderately severe hypogammaglobulinemia (IgG \<450 mg/dL) or Immunoglobulin A (IgA) \<10mg/dL.
6. Positive QuantiFERON -Tuberculosis (TB) Gold test results.
7. Pulmonary fibrotic changes on chest radiograph consistent with prior healed tuberculosis.
8. Active bacterial, viral, fungal, or opportunistic infections.
9. Evidence of infection with human immunodeficiency virus (HIV), hepatitis B (as assessed by HBsAg and anti-HBc) or hepatitis C.
10. Hospitalization for treatment of infections, or parenteral (IV or IM) antibacterials, antivirals, anti-fungals, or anti-parasitic agents within the past 60 days.
11. Chronic infection that is currently being treated with suppressive antibiotic therapy, including but not limited to tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, and atypical mycobacteria.
12. History of significant infection or recurrent infection that, in the investigator's opinion, places the participant at risk by participating in this study.
13. Receipt of a live-attenuated vaccine within 3 months of study enrollment.
14. End-stage renal disease (eGFR \<20 mL/min/1.73m\^2).
15. Concomitant malignancies or a history of malignancy, with the exception of adequately treated basal and squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
16. History of transplantation.
17. History of primary immunodeficiency.
18. Pregnancy.
19. Breastfeeding.
20. Unwillingness to use an FDA-approved form of birth control (including but not limited to a diaphragm, an intrauterine device, progesterone implants or injections, oral contraceptives, the double-barrier method, or a condom).
21. Use of cyclophosphamide within the past 6 months.
22. Use of anti-Tumor Necrosis Factor (TNF) medication, other biologic medications, or experimental non- biologic therapeutic agents within the past 90 days, or 5 half-lives prior to screening, whichever is greater.
23. Intravenous immunoglobulin (IVIG), plasmapheresis, or leukopheresis within the past 90 days.
24. Use of investigational biologic agent within the past 12 months.
25. Prior treatment with rituximab, belimumab, atacicept, or other biologic B cell therapy.
26. Liver function test \[aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase\] results that are \>=2 times the upper limit of normal.
27. Severe, progressive, or uncontrolled renal, hepatic, hematological,gastrointestinal, pulmonary, cardiac, or neurological disease, either related or unrelated to SLE, with the exception of active lupus nephritis (or, in the investigator's opinion, any other concomitant medical condition that places the participant at risk by participating in this study).
28. Comorbidities requiring corticosteroid therapy, including those which have required three or more courses of systemic corticosteroids within the previous 12 months.
29. Current substance abuse or history of substance abuse within the past year.
30. History of severe allergic or anaphylactic reactions to chimeric or fully human monoclonal antibodies.
31. History of anaphylactic reaction to parenteral administration of contrast agents.
32. Lack of peripheral venous access.
33. History of severe depression or severe psychiatric condition.
34. History of suicidal thoughts within the past 2 months or suicidal behavior within the past 6 months, or a significant suicide risk in the investigator's opinion.
35. Inability to comply with study and follow-up procedures.
18 Years
ALL
No
Sponsors
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Immune Tolerance Network (ITN)
NETWORK
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Betty Diamond, M.D.
Role: STUDY_CHAIR
Feinstein Institute for Medical Research
David Wofsy, M.D.
Role: STUDY_CHAIR
University of California San Francisco, Department of Medicine
Maria Dall'Era, M.D.
Role: STUDY_CHAIR
University of California San Francisco, Department of Medicine
Cynthia Aranow, M.D.
Role: STUDY_CHAIR
Feinstein Institute for Medical Research
Locations
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University of Alabama, Birmingham
Birmingham, Alabama, United States
UCLA Medical Center: Division of Rheumatology
Los Angeles, California, United States
University of California, San Francisco
San Francisco, California, United States
University of Colorado Denver: School of Medicine: Division of Rheumatology
Aurora, Colorado, United States
Colorado Kidney Care
Denver, Colorado, United States
Emory University School of Medicine
Atlanta, Georgia, United States
Washington University in St. Louis
St Louis, Missouri, United States
Feinstein Institute, North Shore Hospital
Manhasset, New York, United States
New York University, Langone Medical Center
New York, New York, United States
Weill Cornell Medical College: Hospital for Special Surgery -
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
University of North Carolina School of Medicine:
Chapel Hill, North Carolina, United States
Ohio State University Wexner Medical Center:
Columbus, Ohio, United States
Medical University of South Carolina
Charleston, South Carolina, United States
University of Texas Southwestern
Dallas, Texas, United States
Countries
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References
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Atisha-Fregoso Y, Malkiel S, Harris KM, Byron M, Ding L, Kanaparthi S, Barry WT, Gao W, Ryker K, Tosta P, Askanase AD, Boackle SA, Chatham WW, Kamen DL, Karp DR, Kirou KA, Sam Lim S, Marder B, McMahon M, Parikh SV, Pendergraft WF 3rd, Podoll AS, Saxena A, Wofsy D, Diamond B, Smilek DE, Aranow C, Dall'Era M. Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis. Arthritis Rheumatol. 2021 Jan;73(1):121-131. doi: 10.1002/art.41466. Epub 2020 Dec 1.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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National Institute of Allergy and Infectious Diseases website
Division of Allergy, Immunology, and Transplantation (DAIT)
Immune Tolerance Network (ITN) website
ITN CALIBRATE study website
Other Identifiers
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CALIBRATE
Identifier Type: OTHER
Identifier Source: secondary_id
DAIT ITN055AI
Identifier Type: -
Identifier Source: org_study_id