This multicenter prospective study seeks to determine if daratumumab given, prior to HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus, can prevent pure red blood cell aplasia with an acceptable safety profile in patients with anti-donor red blood cell antibodies, achieving an event-free survival similar to transplanted patients without such antibodies.
Patients with SCD age 2-24.99 years who have a healthy HLA-identical sibling donor with major ABO incompatibility OR patients with RBC alloantibodies against other donor RBC antigens.
Patients must have an absolute neutrophil count of 1 x 109/L and a platelet count of 100 x 109/L.
Lansky/Karnofsky score of, at least, 70.
History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥200 cm/sec by the non-imaging technique measured at a minimum of two separate occasions.
Life expectancy less than 6 month
Pregnant or breastfeeding patients.
Infectious Disease: Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning. Patients with confirmed seropositivity for HIV and patients with active or resolved Hepatitis B or C determined by serology and/or NAAT are excluded.
Liver: Direct (conjugated) bilirubin > 1.5 mg/dL. Transaminases >5x upper limit of normal for age.
Children's National Research Institute
Lead sponsor
Alberta Children's Hospital
Collaborator
The Hospital for Sick Children
Collaborator
Levine Children's Hospital
Collaborator
Ann & Robert H Lurie Children's Hospital of Chicago
Collaborator
Nationwide Children's Hospital
Collaborator
Children's Hospital at Montefiore
Collaborator
Doris Duke Charitable Foundation
Collaborator
Janssen Pharmaceuticals
Collaborator