RH Genotype Matched RBC Transfusions

Sickle Cells Disease Clinical Trial

— RBC  

Official title:

RH Genotype Matched Red Cell Transfusions for Patients With Sickle Cell Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04156893
• Other study ID #: 19-016565
• Secondary ID: R01HL147879R01HL
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 30, 2020
• Est. completion date: October 2029

Study information

• Verified date: May 2024
• Source: Children's Hospital of Philadelphia
• Contact: Stella Chou, MD
• Phone: 215-590-0947
• Email: chous[@]chop.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine the feasibility and efficacy of matching donor red cells by RH genotype for a cohort of chronically transfused patients with SCD.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: October 2029
• Est. primary completion date: April 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cells Disease

Intervention

Biological:
• Red 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.

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	National Heart, Lung, and Blood Institute (NHLBI), New York Blood Center

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. Erratum In: JAMA. 2014 Nov 12;312(18):1932. JAMA. 2015 Feb 17;313(7):729. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the treatment efficacy by monitoring the rate of Rh alloimmunization	A primary objective is to determine whether providing RH genotype matched red cell units can reduce or prevent Rh alloimmunization.	3.5 years
Primary	Determine the feasibility of identifying sufficient RH genotype matched units	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.	3.5 years
Secondary	Determine the rate of non-Rh alloimmunization	A secondary objective is to determine the rate of antibody formation outside the Rh blood group system, such as anti-Kidd or -S/s.	3.5 years