Drug intelligence / Profile preview

cyclophosphamide + siplizumab + cyclosporine + rituximab + prednisone

Development stage
Unknown
Lead developer
National Cancer Institute
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Oral
01

Overview

This conditioning regimen is a multi-component therapeutic protocol developed for patients with end-stage renal disease (ESRD) undergoing simultaneous living related donor kidney and bone marrow transplantation. The regimen was evaluated in the Phase 1 ITN010ST study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It primarily consists of the DNA alkylating agent cyclophosphamide, the anti-CD2 monoclonal antibody siplizumab (MEDI-507), and the calcineurin inhibitor cyclosporine A, combined with thymic irradiation. Later modifications to the protocol added the anti-CD20 antibody rituximab and the corticosteroid prednisone to enhance outcomes and prevent the formation of donor-specific antibodies. The mechanism of action involves profound recipient T-cell and B-cell depletion alongside myelosuppression to facilitate the establishment of mixed hematopoietic chimerism, which aims to induce long-term immune tolerance to the renal allograft and potentially allow for the discontinuation of maintenance immunosuppression.

Other names
ITN010ST conditioning regimenITN-010ST conditioning regimenITN 010ST conditioning regimenMEDI-507 conditioning regimenMEDI507 conditioning regimenMEDI 507 conditioning regimensiplizumab conditioning regimenconditioning regimen-National Institute of Allergy and Infectious Diseases (NIAID)-end-stage renal disease
02

Targets

CD20 (B-lymphocyte antigen CD20)CD2 (T-cell Surface Antigen CD2)PPIA (Peptidyl-prolyl cis-trans isomerase A)GR (Glucocorticoid receptor)DNACN (Calcineurin)

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