Cynthia Aranow | North Shore Hospital | Manhasset, NY
Maria Dall'era | University of California San Francisco | San Francisco, CA
David Wofsy | University of California San Francisco | San Francisco, CA
Columbia University Medical Center: Department of Medicine, Division of Rheumatology | New York, NY
Emory University School of Medicine: Division of Rheumatology | Atlanta, GA
Washington University in St. Louis: Division of Rheumatology | St. Louis, MO
Hospital for Special Surgery, New York: Division of Rheumatology | New York, NY
University of Alabama at Birmingham: Arthritis Clinical Intervention Program | Birmingham, AL
New York University Langone Medical Center: Department of Medicine, Division of Rheumatology | New York, NY
Medical University of South Carolina: MUSC Lupus Erythematous (M.U.S.C.L.E.) Research Group | Charleston, SC
University of Colorado Denver Division of Rheumatology | Aurora, CO
University of North Carolina School of Medicine: Division of Nephrology and Hypertension, Kidney Cen | Chapel Hill, NC
UCLA Medical Center: Division of Rheumatology | Los Angeles, CA
Colorado Kidney Care | Denver, CO
University of California San Francisco School of Medicine: Division of Rheumatology | San Francisco, CA
Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases | Manhasset, NY
Ohio State University Wexner Medical Center: Division of Nephrology | Columbus, OH
University of Texas Southwestern Medical Center: Division of Rheumatic Diseases | Dallas, TX
ITN055AI
Complete
The objective of the CALIBRATE study is to determine if treating lupus nephritis with a combination of rituximab (Rituxan®) and cyclophosphamide (Cytoxan®), or a combination of rituximab and cyclophosphamide followed by treatment with belimumab (Benlysta®) is safe and if this drug combination can block the immune system attacks on the kidney.
Rituximab (anti-CD20) depletes B cells which are known to be key mediators in autoimmune diseases like lupus nephritis. Belimumab is a monoclonal antibody that inhibits B cell activating factor (BAFF), a potent cytokine important for B cell maturation. The rationale for the CALIBRATE trial is based on the observation that BAFF levels are known to be elevated following B cell depletion, and high BAFF levels have been associated with an increased risk of recurrent disease flare. It is likely that the circulating high BAFF levels that exist following B cell depletion permit the maturation of autoreactive B cells, by allowing them to bypass tolerance checkpoints and enter the immune repertoire. B cell reconstitution in the absence of high levels of BAFF might result in a tolerized B cell repertoire without autoreactivity and a sustained clinical response.
This study is a prospective, randomized, open label multicenter study that will enroll 40 adults with active lupus nephritis who are refractory to standard-of-care treatment. Participants will be randomized to two treatment groups: One will receive rituximab and cyclophosphamide followed by belimumab and corticosteroids, and the other will receive rituximab and cyclophosphamide followed by corticosteroids alone. The primary objective is to assess the safety of this regimen, and secondarily will assess clinical responses at weeks 24, 48, and 96, and tolerance (a sustained clinical response) at week 96. In addition, the number of the autoreactive B cells will be assessed at 48 weeks as a unique and important mechanistic correlate of tolerance.
This trial reflects the ITN’s strategy that tolerance induction in autoimmune diseases will likely require a combination of agents that target multiple components of the immune system. The regimen in the CALIBRATE study combines immune cell depletion (rituximab) followed by cytokine blockade (belimumab), with the goal of durably altering the B cell compartment such that autoreactivity is diminished.
You may be eligible to participate in the CALIBRATE Study if you:
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, Lim SS, Marder B, McMahon M, Parikh SV, Pendergraft WF 3rd, Podoll AS, Saxena A, Wofsy D, Diamond B, Smilek DE, Aranow C, Dall'Era M (2020). CALIBRATE: A Phase 2 Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis. Arthritis Rheumatol., 73 (1), 121-131.
Aranow C, Dall'Era M, Byron M, Ding L, Smilek D, Diamond B, Wofsy D (2018). FRI0305 Phase 2 trial of induction therapy with anti-cd20 (RITUXIMAB) followed by maintenance therapy with anti-baff (BELIMUMAB) in patients with active lupus nephritis. Ann Rheum Dis, 690.
