Sickle Cells Disease
Conditions
Keywords
Chronic Transfusion
Brief summary
To determine the feasibility and efficacy of matching donor red cells by RH genotype for a cohort of chronically transfused patients with SCD.
Detailed description
This is a Phase 1/2 trial in patients with Sickle Cell Disease requiring chronic red cell transfusions. RH genotyped donor units will be obtained from the New York Blood Center. Patients will be matched with donor units whose RH genotypes predict no foreign Rh protein exposure to the patient. This will provide red cell matching at a level above the current standard of care (serologic C, E, and K matching). Patients will receive RH matched red cells for the duration of their chronic transfusion therapy or up to three years, whichever is shorter. In the pilot phase, we have determined it is feasible to identify RH matched donor units for the patient's RH genotype for every scheduled transfusion. We will now continue to show feasibility as well as determine efficacy by monitoring Rh alloantibody formation. For subjects with a history of stroke/recurrent transient ischemic attack or other indication who require tight control of Hb S, and RH genotyped blood is not available, standard of care serologic matched blood would be administered rather than delaying transfusion and risking higher Hb S level. For all subjects, standard of care serologic matched blood would be administered rather than delaying transfusion beyond 7 days.
Interventions
BIOLOGICALRed cell units that are genotype matched at the RHD and RHCE loci
Patients will be provided with red cell units that are C, E, and K antigen matched (standard of care for patients with SCD) and genotype matched at the RHD and RHCE loci.
Sponsors
Children's Hospital of Philadelphia
New York Blood Center
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will receive RH genotype matched red cell units for transfusion. For subjects with a history of stroke/recurrent transient ischemic attack or other indication who require tight control of Hb S, and RH genotyped blood is not available, standard of care serologic matched blood would be administered rather than delaying transfusion and risking higher Hb S level. For all subjects, standard of care serologic matched blood would be administered rather than delaying transfusion beyond 7 days
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects age \>6 months * Diagnosis of SCD, all genotypes * Require a period of chronic red cell transfusion therapy * Subject/parental/guardian permission (informed consent) and if appropriate, child assent
Exclusion criteria
* Rare RH genotype that would preclude identification of sufficient RBC units * Antigen negative requirements due to alloimmunization that would preclude identification of sufficient RBC units * Alloimmunized to D antigen * Rh alloimmunized patients for whom providing RH genotype matched blood would expose the patient to an antigen that would not be consistent with standard of care and blood bank protocols * Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the treatment efficacy by monitoring the rate of Rh alloimmunization | 3.5 years | A primary objective is to determine whether providing RH genotype matched red cell units can reduce or prevent Rh alloimmunization. |
| Determine the feasibility of identifying sufficient RH genotype matched units | 3.5 years | A primary objective is to determine the feasibility of identifying sufficient RH genotype matched red cells for chronically transfused patients with SCD with varied RH genotypes. Approximately 20 RHD (Rhesus D) and 20 RHCE (Rhesus CE) variants have been observed in patients with SCD and will determine whether sufficient RH genotyped units can be matched to the patient's own RH genotype. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the rate of non-Rh alloimmunization | 3.5 years | A secondary objective is to determine the rate of antibody formation outside the Rh blood group system, such as anti-Kidd or -S/s. |
Countries
United States
Contacts
CONTACTStella Chou, MD
PRINCIPAL_INVESTIGATORStella Chou, MD
Children's Hospital of Philadelphia
Outcome results
None listed