Sickle Cell Disease Transplant Using a Nonmyeloablative Approach: Adding Daratumumab for Patients With Anti-donor Red Cell AntibodY
Children's National Research Institute
Summary
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.
Description
This study addresses an important question: Can daratumumab safely be administered prior to matched sibling donor (MSD) nonmyeloablative hematopoietic cell transplant (HCT) for SCD to avoid pure red blood cell aplasia in patients at risk of this complication? and thus achieve an event-free survival similar to patients without anti-donor red blood cell (RBC) antibodies? Patients with anti-donor RBC antibodies, which includes patients with major ABO mismatch and other RBC alloantibodies against donor, have largely been excluded from the nonmyeloablative HCT approach given their risk of delayed…
Eligibility
- Age range
- 2–25 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: General: * 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. Patients with genotypes hemoglobin SS and Sβ0 thalassemia must have at least one of the following: * History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥200 cm/sec by the non-imaging technique measured at a mi…
Interventions
- DrugDaratumumab
Daratumumab is a cytotoxic monoclonal antibody (IgG1k) to CD38 and is commercially approved to treat multiple myeloma. CD38 is expressed on several types of blood cells including B-cells, antibody-secreting plasma blasts and plasma cells. As a result, it has been used to treat antibody-mediated diseases, including children with antibody-mediated cytopenias post-HCT.
- DrugAlemtuzumab
Alemtuzumab is a humanized monoclonal antibody specific to lymphocyte antigens. It is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H) that is directed against the 21-28 kD cell surface glycoprotein, CD52.
- DrugSirolimus
Sirolimus is an mTOR inhibitor immunosuppressant used to prevent organ transplant rejections as well as treat lymphangioleiomyomatosis and adults with perivascular epithelioid cell tumors.
- RadiationTotal Body Irradiation
Total body irradiation is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell transplantation. The radiation is given in a low dose so that normal tissues can repair themselves.
Location
- Children's National HospitalWashington D.C., District of Columbia