Comparative Analysis of Biotinylated, Irradiated and 51-Chromium Radiolabeled Red Blood Cells for Analysis of Recovery and Survival After Autologous Transfusion

This research is being done to compare the red blood circulation survival in healthy adult volunteers between the 51 chromium (51Cr) red blood cell (RBC) labeling method and the Biotin (BioRBC) red blood cell (RBC) labeling method to determine if biotinylated red blood cells (BioRBC) is an acceptable non radioactive alternative to 51 chromium (51Cr) radiolabeling for regulatory pharmacokinetic studies of red blood cell products.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteer Red Blood Cell Labeling Study; Not Disease Focused
• Intervention / Treatment: Biological: Biotinylated Red Blood Cells (BioRBC); Biological: 51 Chromium Labeled Red Blood Cells (51Cr RBC); Biological: Technetium 99m Labeled Red Blood Cells (99mTc RBC); Biological: Irradiated Biotinylated Red Blood Cells (Irradiated BioRBC)

Detailed Description

This is a Phase 1, randomized, controlled, autologous transfusion study in healthy adult volunteers designed to compare biotinylated red blood cells (BioRBC) with 51 chromium (51Cr)-labeled red blood cells for the assessment of red blood cell (RBC) recovery and survival after 42 days of storage, with and without irradiation at Day 0.

Both 51Cr and biotin labeling have been used to measure autologous RBC recovery and survival, but biotin has not yet been accepted by the U.S. Food and Drug Administration (FDA) as a method to determine 24 hour post transfusion recovery and long term survival after storage.

Study procedures include screening, blood samples, testing, labeling and transfusion.

It is expected that about 20 people will take part in this research study.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jose A Cancelas-Perez, MD, PhD; Phone Number: 617-632-3446; Email: jose_cancelas-perez@dfci.harvard.edu

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • Hoxworth Blood Center, University of Cincinnati
      • Contact: Neeta Rugg, MS; Phone Number: 513-558-1503; Email: neeta.rugg@uc.edu
      • Principal Investigator: Sachie Ikegami, MD, PhD
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Not yet recruiting
      • American Red Cross
      • Contact: Michael Wellington, MS; Phone Number: (757) 446-7720; Email: michael.wellington@redcross.org
      • Principal Investigator: Bethany Brown, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Signed and dated informed consent form.

  • Age ≥18 years, of either gender.
  • Normal health status (as determined by Investigators' review of medical history and physical exam).
  • Qualifies for a collection; Males: height >5'1" and weight >130 lbs; Females: height >5' 5" and weight > 150 lbs.
  • Complete blood count (CBC; including RBC indices MCV, MCH, MCHC, and RDW) and serum chemistry values within normal limits (including calcium, bicarbonate, chloride, inorganic phosphate, potassium, sodium, cholesterol, glucose, total protein, triglycerides, LDH, ALT, AST, total bilirubin, BUN, creatinine, and ferritin). Values outside of normal reference range if considered not to be clinically significant by the site PI may be allowed as per the site PI.
  • Hemoglobin levels >13.3 g/dL and hematocrit >40% for both male and female subjects.
  • Negative blood donor screening test panel for HIV, HBV, HCV, HTLV, Syphilis, and WNV virus at the time of donation.
  • Female subjects of childbearing potential and male subjects must agree to use a medically acceptable method of contraception throughout the study periods. A barrier method of contraception must be included, regardless of other methods.
  • Meet or exceed AABB guidelines for blood donation, with the exception of travel deferrals as defined by site-specific SOPs.

Exclusion Criteria:

• Known RBC disorder that could affect RBC survival.

  • Treatment with any medication known to affect RBC viability.
  • Pregnant or nursing female.
  • Male subjects or female subjects of childbearing potential not using medically acceptable contraceptive methods.
  • Participation in another clinical study currently or within the past 28 days.
  • Subjects not eligible to provide a double RBC donation per AABB guidelines for blood donation.
  • Subjects who have received blood transfusion within the previous year.
  • Known pre-existing antibody specific to BioRBC.
  • Subjects who have received a previous infusion of BioRBC at any time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Unirradiated Red Blood Cells; Day 42: Samples from each unit are labeled with biotin at one density and 51Cr. Assignments of biotin density and 51-Cr are randomized. Participants are infused with four types of manipulated RBCs (Stored Test (Irradiated), Stored Control (Non-Irradiated), Stored Control or Test RBCs labeled with 51Cr, Fresh RBCs with 99mTc) and one type of unmanipulated RBCs (Non-Irradiated or Irradiated, non-labeled RBCs).	Biological: Biotinylated Red Blood Cells (BioRBC); Intravenous infusion; Other Names: BioRBC; Biotin labeled red blood cells; Biological: 51 Chromium Labeled Red Blood Cells (51Cr RBC); Intravenous infusion; Biological: Technetium 99m Labeled Red Blood Cells (99mTc RBC); Intravenous infusion
Experimental: Gamma Irradiated Red Blood Cells; Day 42: Samples from each unit are labeled with biotin at one density and 51Cr. Assignments of biotin density and 51-Cr are randomized. Participants are infused with four types of manipulated RBCs (Stored Test (Irradiated), Stored Control (Non-Irradiated), Stored Control or Test RBCs labeled with 51Cr, Fresh RBCs with 99mTc) and one type of unmanipulated RBCs (Non-Irradiated or Irradiated, non-labeled RBCs).	Biological: 51 Chromium Labeled Red Blood Cells (51Cr RBC); Intravenous infusion; Biological: Technetium 99m Labeled Red Blood Cells (99mTc RBC); Intravenous infusion; Biological: Irradiated Biotinylated Red Blood Cells (Irradiated BioRBC); Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour Post-transfusion Recovery (PTR24) of Irradiated or Non-irradiated biotinylated Red Blood Cells Compared With 51Cr-Labeled Red Blood Cells	Percentage of infused autologous red blood cells (RBC) remaining in circulation 24 hours after transfusion	Day 1 after completion of autologous RBC infusion (Day 43 of the study)
Lifespan of of Irradiated or Non-irradiated biotinylated Red Blood Cells Compared With 51Cr-Labeled Red Blood Cells	Survival of autologous irradiated RBC expressed as days of RBC present in blood until they disappear from circulation	From immediately post infusion through Day 112 post-infusion (day 154 of the study, at approximately 16 weeks post transfusion).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T50 of Irradiated or Non-irradiated biotinylated Red Blood Cells Compared With 51Cr-Labeled Red Blood Cells	Lifespan of autologous irradiated RBC, expressed as Median lifespan (T50; time in days for 50% of labeled red cells remain in circulation)	From immediately post infusion through Day 112 post-infusion (day 154 of the study, at approximately 16 weeks post transfusion).
Area under the curve (AUC) of Irradiated or Non-irradiated biotinylated Red Blood Cells Compared With 51Cr-Labeled Red Blood Cells	Area under the curve of autologous irradiated RBC, expressed as an integrated area of the parameter time (days) x percentage of remaining cells in circulation	From immediately post infusion through Day 112 post-infusion (day 154 of the study, at approximately 16 weeks post transfusion).
Incidence of Adverse Events and Serious Adverse Events Following Infusion of Biotinylated and Irradiated Biotinylated Red Blood Cells	Number and proportion of subjects experiencing adverse events (AEs) and serious adverse events (SAEs) with specific attention to: Infusion reactions (e.g., fever, chills, rash, hypotension), Suspected transfusion related sepsis, Events meeting protocol defined stopping rules (e.g., hemolysis with anti BioRBC antibody), and Any AE judged possibly, probably, or definitely related to infusion of BioRBC or irradiated BioRBC.	From Day 42 (infusion day) through Day 154 (approximately 16 weeks post transfusion)
Incidence of Antibodies Against Biotinylated Red Blood Cells After Infusion of BioRBC	Proportion of subjects who develop detectable antibodies specific to biotinylated RBC (anti BioRBC) following infusion of BioRBC	From screening (up to 28 days before donation) through Day 112 post infusion (day 154 after red blood cell collection); extended follow up annually if anti BioRBC is detected until it disappears from circulation.

Collaborators and Investigators

• Sponsor: Jose Cancelas
• Collaborators: Department of Health and Human Services
• Investigators: Principal Investigator: Jose A Cancelas-Perez, MD, PhD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 16, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Healthy volunteers; Red blood cell labeling
• Additional Relevant MeSH Terms: Inorganic Chemicals; Elements; Metals; Metals, Heavy; Transition Elements; Elements, Radioactive; Radioisotopes; Isotopes; Technetium
• Other Study ID Numbers: 25-620; 75A50123C00052 (Other Grant/Funding Number: HHS/BARDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No