Clinical trial NCT04156893: RH Genotype Matched RBC Transfusions
Official title: RH Genotype Matched Red Cell Transfusions for Patients With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Sickle Cells Disease
Keywords: Chronic Transfusion
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: New York Blood Center
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-11-08
Enrollment: 35
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determine the treatment efficacy by monitoring the rate of Rh alloimmunization
timeFrame: 3.5 years
measure: Determine the feasibility of identifying sufficient RH genotype matched units
timeFrame: 3.5 years
Secondary outcomes:
measure: Determine the rate of non-Rh alloimmunization
timeFrame: 3.5 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Stella Chou, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chou ST, Jackson T, Vege S, Smith-Whitley K, Friedman DF, Westhoff CM. High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors. Blood. 2013 Aug 8;122(6):1062-71. doi: 10.1182/blood-2013-03-490623. Epub 2013 May 30.
citation: Vichinsky EP, Earles A, Johnson RA, Hoag MS, Williams A, Lubin B. Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood. N Engl J Med. 1990 Jun 7;322(23):1617-21. doi: 10.1056/NEJM199006073222301.
citation: Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517.
citation: Chou ST, Evans P, Vege S, Coleman SL, Friedman DF, Keller M, Westhoff CM. RH genotype matching for transfusion support in sickle cell disease. Blood. 2018 Sep 13;132(11):1198-1207. doi: 10.1182/blood-2018-05-851360. Epub 2018 Jul 19.
citation: Coleman S, Westhoff CM, Friedman DF, Chou ST. Alloimmunization in patients with sickle cell disease and underrecognition of accompanying delayed hemolytic transfusion reactions. Transfusion. 2019 Jul;59(7):2282-2291. doi: 10.1111/trf.15328. Epub 2019 Apr 25.