RHD Genotype Matched Red Cells for Anti-D

NCT04156906 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: 19-016566R01HL147879-01
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sickle Cell Disease; Anti-D Antibodies

Keywords

Chronic Transfusion

Outcome Measures

Primary Outcomes (1)

• Anti-D Recurrence

  To determine safety of providing RH genotype match red cells to patients with a history of anti-D, we observed if anti-D reappearance occurred or evidence of hemolysis of transfused red cells.

  Through study completion and follow-up phase, an average of 10 months per participant

Study Arms (1)

D+ RH genotype matched Red Blood Cell Transfusion

EXPERIMENTAL

Investigators will provide one red cell unit of D+ RH genotype matched RBCs at the first transfusion study visit. The remainder of units will be provided per clinical standard of care, i.e. D-, CEK-matched, and negative for all other antigens the patient is alloimmunized against. If laboratory monitoring shows no reappearance of anti-D and no signs of increased red cell hemolysis, the patient will receive one unit of D+ RH genotype matched RBCs at the 2nd transfusion study visit, and if tolerated, D+ red cell exposures will increase by one unit per study visit until all units required are D+.

Biological: D+ RH genotype matched red cell units for transfusion

Interventions

D+ RH genotype matched red cell units for transfusion BIOLOGICAL

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.

D+ RH genotype matched Red Blood Cell Transfusion

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• New York Blood Center: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (6)

• 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.

  PMID: 23723452 BACKGROUND

• 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.

  PMID: 2342522 BACKGROUND

• 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.

  PMID: 25203083 BACKGROUND

• 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.

  PMID: 30026182 BACKGROUND

• 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.

  PMID: 28388467 BACKGROUND

• Chou ST, Mewha J, Friedman DF, Lazariu V, Makrm S, Ochoa G, Vege S, Westhoff CM. Genotyped RhD+ red cells for D-positive patients with sickle cell disease with conventional RHD and unexpected anti-D. Blood. 2024 Nov 7;144(19):2045-2049. doi: 10.1182/blood.2024025602.

  PMID: 39172743 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Blood Transfusion

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Results Point of Contact

• Title: Stella Chou, MD
• Organization: The Children's Hospital of Philadelphia

chous@chop.edu

215-590-0947

Study Officials

• Stella Chou, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2019
• First Posted: November 8, 2019
• Study Start: July 8, 2020
• Primary Completion: March 4, 2024
• Study Completion: October 4, 2024
• Last Updated: May 2, 2025
• Results First Posted: May 2, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: For the duration of the study
• Access Criteria: Only study team members will have access to the data

Locations

US (1)