Lupus NephritisPhase 2CALIBRATENCT02260934
Rituximab and Belimumab for Lupus Nephritis
A Phase 2 study testing Rituximab, Cyclophosphamide and Prednisone in people with Lupus Nephritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
Trial summary
In this experimental study, researchers will try to find out if treatment of lupus nephritis with a combination of rituximab and cyclophosphamide (CTX), or a combination of rituximab and CTX followed by treatment with belimumab is safe and if this drug combination can block the immune system attacks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lupus Nephritis
- What is being tested?
- Rituximab, Cyclophosphamide and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 15 sitesUnited States
- Study dates
- 9 Jul 2015to 8 Feb 2019
- Phase
- Phase 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
- Diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria.
- Positive antinuclear antibody (ANA) or positive anti-ds DNA test results at visit -1 or any time within 14 days before visit -1.
- 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;
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- >5 White blood cell per high powered field (WBC/hpf) in the absence of infection; or
- Cellular casts limited to RBC or WBC casts.
- Urine protein-to-creatinine ratio (UPCR) >1 at study entry based on a 24-hour collection.
- Ability to provide informed consent.
Who cannot join
- New onset lupus nephritis, defined as lupus nephritis for which the participant has not yet been treated with either mycophenolate mofetil or cyclophosphamide.
- Neutropenia (absolute neutrophil count <1500/mm^3).
- Thrombocytopenia (platelets <50,000/mm^3).
- Moderately severe anemia (Hgb < mg/dL).
- Moderately severe hypogammaglobulinemia (IgG <450 mg/dL) or Immunoglobulin A (IgA) <10mg/dL.
- Positive QuantiFERON -Tuberculosis (TB) Gold test results.
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- Pulmonary fibrotic changes on chest radiograph consistent with prior healed tuberculosis.
- Active bacterial, viral, fungal, or opportunistic infections.
- Evidence of infection with human immunodeficiency virus (HIV), hepatitis B (as assessed by HBsAg and anti-HBc) or hepatitis C.
- Hospitalization for treatment of infections, or parenteral (IV or IM) antibacterials, antivirals, anti-fungals, or anti-parasitic agents within the past 60 days.
- 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.
- History of significant infection or recurrent infection that, in the investigator's opinion, places the participant at risk by participating in this study.
- Receipt of a live-attenuated vaccine within 3 months of study enrollment.
- End-stage renal disease (eGFR <20 mL/min/1.73m^2).
- 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.
- History of transplantation.
- History of primary immunodeficiency.
- Pregnancy.
- Breastfeeding.
- 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).
- Use of cyclophosphamide within the past 6 months.
- 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.
- Intravenous immunoglobulin (IVIG), plasmapheresis, or leukopheresis within the past 90 days.
- Use of investigational biologic agent within the past 12 months.
- Prior treatment with rituximab, belimumab, atacicept, or other biologic B cell therapy.
- Liver function test [aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase] results that are >=2 times the upper limit of normal.
- 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).
- Comorbidities requiring corticosteroid therapy, including those which have required three or more courses of systemic corticosteroids within the previous 12 months.
- Current substance abuse or history of substance abuse within the past year.
- History of severe allergic or anaphylactic reactions to chimeric or fully human monoclonal antibodies.
- History of anaphylactic reaction to parenteral administration of contrast agents.
- Lack of peripheral venous access.
- History of severe depression or severe psychiatric condition.
- 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.
- Inability to comply with study and follow-up procedures.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Emory University School of Medicine
Atlanta, Georgia, 30303
University of Colorado Denver: School of Medicine: Division of Rheumatology
Aurora, Colorado, 80045
University of Alabama, Birmingham
Birmingham, Alabama, 35294
University of North Carolina School of Medicine:
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Ohio State University Wexner Medical Center:
Columbus, Ohio, 43213
University of Texas Southwestern
Dallas, Texas, 75390
Colorado Kidney Care
Denver, Colorado, 80218
UCLA Medical Center: Division of Rheumatology
Los Angeles, California, 90095
Feinstein Institute, North Shore Hospital
Manhasset, New York, 10030
New York University, Langone Medical Center
New York, New York, 10016
Weill Cornell Medical College: Hospital for Special Surgery -
New York, New York, 10021
Columbia University Medical Center
New York, New York, 10032
University of California, San Francisco
San Francisco, California, 94143
Washington University in St. Louis
St Louis, Missouri, 36110
About this study
Official title: Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis (ITN055AI)
In this experimental study, researchers will try to find out if treatment of lupus nephritis with a combination of rituximab and cyclophosphamide (CTX), or a combination of rituximab and CTX followed by treatment with belimumab is safe and if this drug combination can block the immune system attacks.
Read the detailed description
Lupus nephritis is a severe form of systemic lupus erythematosus (SLE) with active disease in the kidneys. SLE is a complex disease in which the body's own immune system attacks some of the body parts: the skin, the joints, the kidneys, the nervous system, the heart, the lungs and the blood. The cause of SLE is not known. Treatment for SLE usually involves drugs that are designed to block the immune system attacks. When SLE affects the kidneys (nephritis), stronger immune suppressing treatment is usually needed.
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
- Lupus Nephritis
- Being tested
- Rituximab, Cyclophosphamide, Prednisone, Methylprednisolone, Diphenhydramine
- Medical subject headings
- Lupus Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabBiological
Also called Rituxan
Rituximab 1000mg intravenously (IV) at week 0 and week 2
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2.
PrednisoneDrug
Also called Deltasone
- 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
Also called Solu-Medrol
Week 0 and Week 2:
Solumedrol (100 mg) IV
DiphenhydramineDrug
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.
AcetaminophenDrug
Also called Tylenol
Acetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
RituximabBiological
Also called Rituxan
Rituximab 1000mg intravenously (IV) at week 0 and week 2.
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2.
PrednisoneDrug
Also called Deltasone
- 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
Also called Solu-Medrol
Week 0 and Week 2: Solumedrol (100 mg) IV
DiphenhydramineDrug
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.
AcetaminophenDrug
Also called Tylenol
Acetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab.
BelimumabBiological
Also called Benlysta
The RCB Group will receive IV belimumab 10mg/kg at weeks 4, 6, 8, and then every 4 weeks through week 48
| Study group | Role | What they receive |
|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Active comparator | Prednisone taper to 10 mg/day by week 12 and continue prednisone 10 mg/day to week 96. Receives: Biological: Rituximab; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Methylprednisolone; Drug: Diphenhydramine; Drug: Acetaminophen |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Experimental | 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. Receives: Biological: Rituximab; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Methylprednisolone; Drug: Diphenhydramine; Drug: Acetaminophen; Biological: Belimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96
The percentage of participants who experienced at least one Grade 3 or higher treatment-emergent infectious adverse event. The severity of adverse events (AEs) was classified into grades using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v4.03:June 14, 2010). Treatment-emergent AEs are those:
- with an onset date on or after the first dose of study medication,
- with onset before first dose but that worsened in severity after first dose, and
- for which the start of the AE in relation to the start of study medication could not be established.
AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 17.0. Grade 3 or higher AEs were classified infectious based on the study team's review of the MedDRA body systems and preferred terms of the AEs.
Measured: Week 0 to Week 96
Secondary outcomes (14)
Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96
The percentage of participants who achieved B cell reconstitution, defined as a peripheral blood total B cell count ≥ to the baseline count or the lower limit of normal, whichever was lower. Note: B cell depletion was expected to occur in this study between Weeks 0 and 4, after initiation of rituximab and cyclophosphamide.
Normal peripheral blood B Cell count: 107 to 698 cells/µL.
Measured: Week 24, Week 48 and Week 96
Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96
The percentage of participants who experienced Grade 4 hypogammaglobulinemia, defined as having a serum Immunoglobulin G (IgG) level < 300 mg/dL. Severity of adverse events (AEs) was classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v4.03:June 14, 2010).
Measured: Week 24, Week 48 and Week 96
Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96
The percentage of participants who achieved a complete response, defined as meeting all of the following criteria:
- Urine protein-to-creatinine ratio (UPCR) < 0.5, based on a 24-hour collection;
- Estimated glomerular filtration rate (eGFR) ≥ 120 ml/min/1.73 m^2 calculated by the CKD-EPI formula or, if < 120 ml/min/1.73 m^2, then > 80% of eGFR at entry; and
- Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.
Measured: Week 24, Week 48 and Week 96
Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96
The percentage of participants who achieved an overall response, defined as meeting all of the following criteria:
- >50% improvement in the urine protein-to-creatinine ratio (UPCR) from study entry, based on a 24-hour collection;
- Estimated glomerular filtration rate (eGFR) ≥120 ml/min/1.73 m^2 calculated by the CKD-EPI formula or, if < 120 ml/min/1.73 m^2, then > 80% of eGFR at entry; and
- Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.
Measured: Week 24, Week 48 and Week 96
Percentage of Participants With a Sustained Complete Response
The percentage of participants who achieved a sustained complete response, defined as a complete response achieved at Week 48 and Week 96.
Complete response was defined as meeting all of the following criteria:
- Urine protein-to-creatinine ratio (UPCR) < 0.5, based on a 24-hour collection;
- Estimated glomerular filtration rate (eGFR) ≥120 ml/min/1.73 m^2 calculated by the CKD-EPI formula or, if < 120 ml/min/1.73 m^2, then > 80% of eGFR at entry; and
- Prednisone dose tapered to 10 mg/day and adherence to prednisone dosing provisions.
Measured: Week 48, Week 96
Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96
The percentage of participants who met the criteria for treatment failure, defined by withdrawal from the protocol treatment regimen due to worsening nephritis, infection, or study medication toxicity.
Measured: Week 24, Week 48 and Week 96
Count of Participants: Frequency of Non-renal Flares by Week 24
Count of participants who experienced non-renal flares, defined as any new "A" finding in a non-renal organ system in the British Isles Lupus Assessment Group (BILAG) assessment. A BILAG "A" finding represents a significant increase in, or a new manifestation of, disease activity.
Measured: Week 24
Count of Participants: Frequency of Non-renal Flares by Week 48
Count of participants who experienced non-renal flares, defined as any new "A" finding in a non-renal organ system in the British Isles Lupus Assessment Group (BILAG) assessment. A BILAG "A" finding represents a significant increase in, or a new manifestation of, disease activity.
Measured: Week 48
Count of Participants: Frequency of Non-renal Flares by Week 96
Count of participants who experienced non-renal flares, defined as any new "A" finding in a non-renal organ system in the British Isles Lupus Assessment Group (BILAG) assessment. A BILAG "A" finding represents a significant increase in, or a new manifestation of, disease activity.
Measured: Week 96
Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96
The percentage of participants who were anti-double stranded DNA (anti-dsDNA) negative, defined as having anti-dsDNA levels <30 IU/mL.
Anti-dsDNA levels are associated with systemic lupus erythematosus disease activity.
Measured: Week 24, Week 48 and Week 96
Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96
The percentage of participants who were hypocomplementemic for complement component, C3, defined as a C3 level <90 mg/dL.
Serum C3 complement is a protein which can be measured in the blood. Low blood levels of C3 are common in those with active lupus.
Measured: Week 24, Week 48 and Week 96
Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96
The percentage of participants who were hypocomplementemic for complemen component C4, defined as a C4 level <10 mg/dL.
Serum C4 complement is a protein which can be measured in the blood. Low blood levels of C4 are common in those with active lupus.
Measured: Week 24, Week 48 and Week 96
Frequency of Specific Adverse Events of Interest By Event by Week 96
Number of ≥ Grade 2 specific treatment-emergent adverse events (AEs) of interest. Grade 2 or higher AEs were classified according to the listed categories of interest based on the study team's review of the AEs.
Treatment-emergent AEs are those:
- with an onset date on or after the first dose of study medication,
- with onset before first dose but that worsened in severity after first dose, and
- for which the start of the AE in relation to the start of study medication could not be established.
The severity of AEs was classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v4.03: June 14, 2010). AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 17.0.
Measured: Week 96
Frequency of Specific Adverse Events of Interest By Participant, By Week 96
Number of participants who experienced ≥Grade 2 specific treatment-emergent adverse events (AEs) of interest. Grade 2 or higher AEs were classified according to the listed categories of interest based on the study team's review of the AEs.
Treatment-emergent AEs are those:
- with an onset date on or after the first dose of study medication,
- with onset before first dose but that worsened in severity after first dose, and
- for which the start of the AE in relation to the start of study medication could not be established.
The severity of AEs was classified using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v4.03: June 14, 2010). AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 17.0.
Measured: Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2014 (estimated)
- Study start9 Jul 2015
- Primary completion12 Mar 2018
- Study completion8 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lupus NephritisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Responsible party
- Sponsor
- Investigators
- Betty Diamond, M.D., Study chair, Feinstein Institute for Medical ResearchDavid Wofsy, M.D., Study chair, University of California San Francisco, Department of MedicineMaria Dall'Era, M.D., Study chair, University of California San Francisco, Department of MedicineCynthia Aranow, M.D., Study chair, Feinstein Institute for Medical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02260934
- Sponsor's protocol ID
- DAIT ITN055AI
- Other IDs
- CALIBRATE
- Acronym
- CALIBRATE
- Status last verified
- Nov 2020
- First submitted
- 6 Oct 2014
- Last updated
- 1 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Participant level data access will be made available to the public at some point in the future via the mechanisms of : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.
Publications
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.
PubMed 32755035Yang Z, Liu S, Zong Z, Li Q, Yu L, Sun S. Treatment of thrombotic microangiopathy associated with systemic lupus erythematosus with low-dose rituximab as an induction agent and belimumab as a maintenance agent. BMC Pediatr. 2025 Feb 26;25(1):141. doi: 10.1186/s12887-025-05506-x.
PubMed 40001033
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis (ITN055AI)
- ClinicalTrials.gov ID
- NCT02260934
- Acronym / sponsor ID
- CALIBRATE / DAIT ITN055AI
- Conditions
- Lupus Nephritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Study start
- 9 Jul 2015 (actual)
- Primary completion
- 12 Mar 2018 (actual)
- Study completion
- 8 Feb 2019 (actual)
- First posted
- 9 Oct 2014 (estimated)
- Results
- Posted 8 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this experimental study, researchers will try to find out if treatment of lupus nephritis with a combination of rituximab and cyclophosphamide (CTX), or a combination of rituximab and CTX followed by treatment with belimumab is safe and if this drug combination can block the immune system attacks.
Detailed description
Lupus nephritis is a severe form of systemic lupus erythematosus (SLE) with active disease in the kidneys. SLE is a complex disease in which the body's own immune system attacks some of the body parts: the skin, the joints, the kidneys, the nervous system, the heart, the lungs and the blood. The cause of SLE is not known. Treatment for SLE usually involves drugs that are designed to block the immune system attacks. When SLE affects the kidneys (nephritis), stronger immune suppressing treatment is usually needed.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab/Cyclophosphamide (RC) | Active comparator | Biological: Rituximab, Drug: Cyclophosphamide, Drug: Prednisone, Drug: Methylprednisolone, Drug: Diphenhydramine, Drug: AcetaminophenPrednisone taper to 10 mg/day by week 12 and continue prednisone 10 mg/day to week 96. |
| Rituximab/Cyclophosphamide/Belimumab (RCB) | Experimental | Biological: Rituximab, Drug: Cyclophosphamide, Drug: Prednisone, Drug: Methylprednisolone, Drug: Diphenhydramine, Drug: Acetaminophen, Biological: Belimumab1. 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria.
- Positive antinuclear antibody (ANA) or positive anti-ds DNA test results at visit -1 or any time within 14 days before visit -1.
- Active proliferative lupus nephritis, as defined by either of the following:
- Urine protein-to-creatinine ratio (UPCR) >1 at study entry based on a 24-hour collection.
- Ability to provide informed consent.
Key exclusion criteria (35 listed)
- New onset lupus nephritis, defined as lupus nephritis for which the participant has not yet been treated with either mycophenolate mofetil or cyclophosphamide.
- Neutropenia (absolute neutrophil count <1500/mm^3).
- Thrombocytopenia (platelets <50,000/mm^3).
- Moderately severe anemia (Hgb < mg/dL).
- Moderately severe hypogammaglobulinemia (IgG <450 mg/dL) or Immunoglobulin A (IgA) <10mg/dL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: RituxanRituximab 1000mg intravenously (IV) at week 0 and week 2 | Biological | Rituximab/Cyclophosphamide (RC) |
| CyclophosphamideAlso: CytoxanCyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2. | Drug | Rituximab/Cyclophosphamide (RC) |
| PrednisoneAlso: Deltasone* 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 | Drug | Rituximab/Cyclophosphamide (RC) |
| MethylprednisoloneAlso: Solu-MedrolWeek 0 and Week 2: Solumedrol (100 mg) IV | Drug | Rituximab/Cyclophosphamide (RC) |
| DiphenhydramineDiphenhydramine (50 mg, or equivalent dose of similar antihistamine) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab. | Drug | Rituximab/Cyclophosphamide (RC) |
| AcetaminophenAlso: TylenolAcetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab. | Drug | Rituximab/Cyclophosphamide (RC) |
| RituximabAlso: RituxanRituximab 1000mg intravenously (IV) at week 0 and week 2. | Biological | Rituximab/Cyclophosphamide/Belimumab (RCB) |
| CyclophosphamideAlso: CytoxanCyclophosphamide (750 mg) intravenously (IV) at week 0 and week 2. | Drug | Rituximab/Cyclophosphamide/Belimumab (RCB) |
| PrednisoneAlso: Deltasone* 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 | Drug | Rituximab/Cyclophosphamide/Belimumab (RCB) |
| MethylprednisoloneAlso: Solu-MedrolWeek 0 and Week 2: Solumedrol (100 mg) IV | Drug | Rituximab/Cyclophosphamide/Belimumab (RCB) |
| DiphenhydramineDiphenhydramine (50 mg, or equivalent dose of similar antihistamine) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab. | Drug | Rituximab/Cyclophosphamide/Belimumab (RCB) |
| AcetaminophenAlso: TylenolAcetaminophen (650 mg) will be given orally 1 hour (plus or minus 15 minutes) before each infusion of rituximab. | Drug | Rituximab/Cyclophosphamide/Belimumab (RCB) |
| BelimumabAlso: BenlystaThe RCB Group will receive IV belimumab 10mg/kg at weeks 4, 6, 8, and then every 4 weeks through week 48 | Biological | Rituximab/Cyclophosphamide/Belimumab (RCB) |
Primary outcome
Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96
Time frame: Week 0 to Week 96
The percentage of participants who experienced at least one Grade 3 or higher treatment-emergent infectious adverse event. The severity of adverse events (AEs) was classified into grades using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, v4.03:June 14, 2010). Treatment-emergent AEs are those: * with an onset date on or after the first dose of study medication, * with onset before first dose but that worsened in severity after first dose, and * for which the start of the AE in relation to the start of study medication could not be established. AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 17.0. Grade 3 or higher AEs were classified infectious based on the study team's review of the MedDRA body systems and preferred terms of the AEs.
14 secondary outcomes
Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96
Time frame: Week 24, Week 48 and Week 96
Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96
Time frame: Week 24, Week 48 and Week 96
Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96
Time frame: Week 24, Week 48 and Week 96
Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96
Time frame: Week 24, Week 48 and Week 96
Percentage of Participants With a Sustained Complete Response
Time frame: Week 48, Week 96
Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96
Time frame: Week 24, Week 48 and Week 96
Count of Participants: Frequency of Non-renal Flares by Week 24
Time frame: Week 24
Count of Participants: Frequency of Non-renal Flares by Week 48
Time frame: Week 48
Count of Participants: Frequency of Non-renal Flares by Week 96
Time frame: Week 96
Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96
Time frame: Week 24, Week 48 and Week 96
Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96
Time frame: Week 24, Week 48 and Week 96
Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96
Time frame: Week 24, Week 48 and Week 96
Frequency of Specific Adverse Events of Interest By Event by Week 96
Time frame: Week 96
Frequency of Specific Adverse Events of Interest By Participant, By Week 96
Time frame: Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 32755035Atisha-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.
- Derived from this study: PubMed 40001033Yang Z, Liu S, Zong Z, Li Q, Yu L, Sun S. Treatment of thrombotic microangiopathy associated with systemic lupus erythematosus with low-dose rituximab as an induction agent and belimumab as a maintenance agent. BMC Pediatr. 2025 Feb 26;25(1):141. doi: 10.1186/s12887-025-05506-x.
- National Institute of Allergy and Infectious Diseases websiteLink provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Immune Tolerance Network (ITN) websiteLink provided by the sponsor.
- ITN CALIBRATE study websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Participant level data access will be made available to the public at some point in the future via the mechanisms of : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Betty Diamond, M.D. study chair
Feinstein Institute for Medical Research
David Wofsy, M.D. study chair
University of California San Francisco, Department of Medicine
Maria Dall'Era, M.D. study chair
University of California San Francisco, Department of Medicine
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab, Cyclophosphamide and Prednisone in people with Lupus Nephritis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
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 35 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 1 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 phase mean?
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 8 Apr 2019). 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?
Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 (time frame: Week 0 to Week 96). 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 NCT02260934, which also lists 2 linked publications.
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 1 Dec 2020.