RH Genotype Matched RBC Transfusions (RBC)

• ClinicalTrials.gov Identifier: NCT04156893
• Recruitment Status: Recruiting
• First Posted: November 8, 2019
• Last Update Posted: August 11, 2022
• Sponsor: Children's Hospital of Philadelphia
• Collaborators: New York Blood Center; National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Children's Hospital of Philadelphia

Tracking Information

• First Submitted Date: November 6, 2019
• First Posted Date: November 8, 2019
• Last Update Posted Date: August 11, 2022
• Actual Study Start Date: January 30, 2020
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 7, 2019)

Feasibility of identifying sufficient RH genotype matched units [ Time Frame: 5.5 years ]

The primary objective of this study is to determine the feasibility of RH genotype matched red cells for chronically transfused patients with SCD. 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.

Original Primary Outcome Measures (submitted: November 6, 2019)

Feasibility of identifying sufficient RH genotype matched units [ Time Frame: 5.5 years ]

The primary objective of this study is to determine the feasibility of RH genotype matched red cells for chronically transfused patients with SCD. Approximately 20 RHD (Rhesus D) and 20 RHCE (Rhesus CE) variants have been observed in patients with SCD, and we will determine whether sufficient RH genotyped units can be matched to the patient's own RH genotype.

Current Secondary Outcome Measures (submitted: November 6, 2019)

Determine the occurrence of Rh alloimmunization [ Time Frame: 5.5 years ]

The secondary objective is to determine if there is a relationship between providing RH genotype matched red cell units to Rh alloimmunization. Although not powered to determine effectiveness, our secondary objective is to monitor for Rh alloimmunization.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: RH Genotype Matched RBC Transfusions
• Official Title: RH Genotype Matched Red Cell Transfusions for Patients With Sickle Cell Disease
• Brief Summary: To determine the feasibility of matching donor red cells by RH genotype for a cohort of chronically transfused patients with SCD.

Detailed Description

This is a pilot feasibility study 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 five years, whichever is shorter. It will then be determined whether sufficient RH matched donor units can be identified for the patient's RH genotype. Although not powered to determine effectiveness, all patients's Rh alloantibody formation will be monitored.

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.

• Study Type: Interventional
• Study Phase: Early Phase 1

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
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

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: 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.

Study Arms

Experimental: RH genotype matched red cell transfusions

Subjects will receive RH genotyped matched red cell units for transfusion in addition to standard serologic C, E, and K antigen matching and being hemoglobin S negative, which is our institutional standard of care for patients with Sickle Cell Disease.

Intervention: Biological: Red cell units that are genotype matched at the RHD and RHCE loci

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 6, 2019): 35
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects age >12 months
• Diagnosis of SCD, all genotypes
• Require a period of chronic red cell transfusion therapy

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Stella Chou, MD; 215-590-0947; chous@chop.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04156893
• Other Study ID Numbers: 19-016565; R01HL147879-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Children's Hospital of Philadelphia
• Original Responsible Party: Same as current
• Current Study Sponsor: Children's Hospital of Philadelphia
• Original Study Sponsor: Same as current

Collaborators

• New York Blood Center
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Stella Chou, MD; Children's Hospital of Philadelphia

• PRS Account: Children's Hospital of Philadelphia
• Verification Date: August 2022