Trial Outcomes & Findings for Siplizumab for Sickle Cell Disease Transplant (NCT NCT06078696)

Siplizumab for Sickle Cell Disease Transplant

Failure rate is a safety endpoint. Failure rate is defined as: graft failure (Primary Graft Rejection: Primary graft rejection is defined as the absence of donor cells (% donor cells \< 5%) assessed by bone marrow or peripheral blood chimerism assays by Day 42. Late Graft Rejection: The absence (\<5%) of donor hematopoietic cells in peripheral blood or bone marrow beyond Day 42 in a patient who had initial evidence of hematopoietic recovery with \> 20% donor cells will be considered a late graft rejection.); or grades III-IV GVHD (as assessed by Center for International Blood and Marrow Transplant Research (CIBMTR) and NIH Consensus Criteria); or death at 100 days.

Time to neutrophil engraftment is defined as the first of 3 measurements on consecutive days when the patient has an absolute neutrophil count of 500/μL after conditioning. Time to platelet engraftment will be defined as the first day of a minimum of 3 measurements on different days that the patient has achieved a platelet count \> 50,000/μL AND did not receive a platelet transfusion in the previous 7 days. Time to red cell engraftment is defined as the first of two measurements on different days that the patient has achieved an absolute reticulocyte count \> 30,000/μL following conditioning regimen induced nadir.

Incidence of acute and chronic GVHD of any grade as evaluated according to the CIBMTR and NIH criteria respectively.

Incidence of other transplant related toxicities, including Veno-occlusive disease (VOD), Idiopathic pneumonia syndrome (IPS), Central nervous system (CNS) toxicity, or Posterior reversible encephalopathy syndrome (PRES).

Significant infections will be recorded including but not limited to bacterial or fungal sepsis, cytomegalovirus (CMV) reactivation with/without clinical disease, adenovirus infection, epstein-barr virus (EBV) reactivation with or without post-transplant lymphoproliferative disorders (PTLD), other significant viral reactivations or community-acquired viral infections and invasive mold infections.

Chimerism is a measure of the engraftment of donor cells within the recipient and is expressed as the percentage ratio between the number of donor cells and recipient cells. Chimerism will be determined by Short Tandem Repeat analysis.

Peripheral blood quantitative assessment of the main lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+, and CD16+/56+). Lymphocytes will be assessed by flow cytometry. In addition, quantitative immunoglobulins will be measured for Immunoglobulin A (IgA), Immunoglobulin M (IgM) and Immunoglobulin (IgG). These will be performed at Day +60 (±10 days) as well as at 1 year (+/- 2 weeks) and after long term follow up at the discretion of the investigator. Descriptive statistics will be used to describe the percentage of patient who are able to achieve reconstitution of important lymphocyte subsets and B cell function at the defined timepoint above.