RHD Genotype Matching for Anti-D

Sickle Cell Disease Clinical Trial

Official title:

RH Genotype Matched Red Cells for Patients With Sickle Cell Disease and Anti-D

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04156906
• Other study ID #: 19-016566
• Secondary ID: R01HL147879-01
• Status: Recruiting
• Phase: Early Phase 1
• Start date: July 8, 2020
• Est. completion date: July 2025

Study information

• Verified date: August 2023
• 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

This is a pilot study to evaluate the feasibility and safety of providing RH genotype matched D+ Red Blood Cells (RBCs) to chronically transfused patients with sickle cell disease (SCD) who type D+ but have formed anti-D and are currently transfused with D- RBC (Red Blood Cell) units.

Description:

Red blood cell transfusion remains a critical therapy for patients with sickle cell disease (SCD). A major problem is the high rate of alloimmunization (antibody formation against transfused red cells) that occurs in patients with SCD. Recent studies performed by Investigators and others demonstrate RH genetic variants in patients and donors is a major risk factor leading to Rh alloimmunization. Anti-D formation in D+ patients occurs frequently, and once identified, providing D- cells for all subsequent transfusions can be challenging. These anti-D antibodies in D+ patients suggest exposure to different or variant D protein on donor cells. Investigators will test whether transfusion of patients with anti-D with RHD genotyped matched red cells is feasible, safe and can decrease D- donor unit demand.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

Inclusion Criteria:

• Subjects age > 8 years old
• Diagnosis of SCD, all genotypes
• Require chronic red cell transfusion therapy
• History of anti-D
• RH genotype predicts D+ expression

Exclusion Criteria:

• Rare RH genotype that would preclude sufficient RBC units
• Antigen negative requirements due to alloimmunization that would preclude sufficient RBC units

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Anti-D Antibodies
• Sickle Cell Disease

Intervention

Biological:
• D+ RH genotype matched red cell units for transfusion
Chronically transfused patients with SCD and anti-D will receive D+ RH genotyped matched red cell units for transfusion in addition to standard C, E, and K antigen matching and being hemoglobin S negative, which is the Children's Hospital of Philadelphia institutional standard of care for patients with SCD. RH genotyping of donor units will be performed by the New York Blood Center (NYBC) Immunogenetics laboratory.

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

Dezan MR, Ribeiro IH, Oliveira VB, Vieira JB, Gomes FC, Franco LAM, Varuzza L, Ribeiro R, Chinoca KZ, Levi JE, Krieger JE, Pereira AC, Gualandro SFM, Rocha VG, Mendrone-Junior A, Sabino EC, Dinardo CL. RHD and RHCE genotyping by next-generation sequencing is an effective strategy to identify molecular variants within sickle cell disease patients. Blood Cells Mol Dis. 2017 Jun;65:8-15. doi: 10.1016/j.bcmd.2017.03.014. Epub 2017 Mar 31. — 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	Feasibility and safety of providing RH genotype matched D+ RBCs to patients with SCD who type D+ but have formed anti-D	To determine feasibility of identifying sufficient RH genotype matched units (identifying sufficient RH genotype match red cells without delays in transfusion), and safety (no anti-D reappearance or evidence of hemolysis of transfused red cells).	5 years