A Phase II Controlled Trial of Allogeneic Mesenchymal Stem Cells for the Treatment of Refractory Lupus

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This a Type 4 clinical trial extension for the MSC in SLE (MiSLE) trial to determine if MSCs provide a safe and effective alternative to current therapies in lupus. The proposed extension will enable completion of the data cleaning, statistical analysis and mechanistic studies. The monetary support for patient visits and MSC preparation is provided by the Lupus Foundation of America in a relatively unique collaborative arrangement making this trial possible. The five years of NIAID support end on 03/31/2023. A No Cost Extension was granted allowing carryover of funds to continue the trial and its components while awaiting the hoped for Title 4 approval. This extension is needed to offset the delays in enrollment in the trial due to the COVID pandemic. Enrollment slowed as the pandemic began due to patient concerns for coming to a medical center. The trial was closed to enrollment in abiding by local IRB determinations. Even after re-opening enrollment was slowed by ongoing patient concerns. Over the last 3-4 months enrollment has returned to pre-COVID rates. At this time, 56/81 patients are infused with investigational product in a 2/1 ratio of MSCs versus placebo in a double blind enrollment and randomization. We propose to complete enrollment in the first 12-18 months of the extension, with completion of the data analysis and mechanistic studies by the 36 month end of the extension. All aspects of the trial including recruitment, consent, infusion, followup, data entry and biologic sample handling have met pretrial goals. We added two new sites (Feinstein and Oklahoma Medical Research Foundation) to enhance enrollment. Our current enrollment rate is 2 patients per month. The two original aims of the study remain unchanged. Aim one is to complete the multicenter double blind placebo controlled trial of MSCs in standard of care refractory lupus patients. Aim two is to perform in depth immune phenotype of the patients pre and post treatment to determine the impacts of MSC infusions on B cell, T cell and mononuclear cell phenotypes and function. This trial will provide insight into the safety and efficacy of MSC infusion in lupus either confirming the positive results in unblinded trials from China. Mechanistic studies will inform immune mechanisms of MSCs.