Clinical trial NCT05255445: Red Blood Cell - IMProving trAnsfusions for Chronically Transfused Recipients
Official title: Red Blood Cell - IMProving trAnsfusions for Chronically Transfused Recipients (RBC-IMPACT)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sickle Cell Disease
Thalassemia
Pediatric Cancer
Keywords: Transfusion
Red Blood Cell
Sickle Cell Disease
Thalassemia
Pediatric
Oncology
RBC survival
Genetic
Non-genetic
Observational
Blood donor
Lead sponsor: Westat
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-02-24
Enrollment: 157
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All transfused patients with sickle cell disease (in the U.S or Brazil) and thalassemia on simple chronic transfusion (or partial manual exchange transfusion) from hospitals affiliated with REDS-IV-P Domestic hubs or Brazil hemocenters. (Aim #1)

Chronically transfused patients with sickle cell disease or thalassemia, and patients with pediatric oncology diagnoses with hypo-proliferative bone marrow receiving care at hospitals affiliated with REDS-IV-P Domestic hubs or Brazil hemocenters (for SCD only). (Aim #2).

Brief summary: Red Blood Cell - IMProving trAnsfusions for Chronically Transfused recipients (RBC-IMPACT) is an observational cohort study to assess donor, component, and recipient factors that contribute to RBC efficacy in chronically and episodically transfused patients. The objective of the study is to determine how specific genetic and non-genetic factors in donors and recipients may impact RBC survival after transfusion - in short, what factors on both the donor and recipient side may improve the efficacy of the transfusion.

Detailed description: Sickle cell disease (SCD) and thalassemia are genetic disorders inducing anemia of differing pathophysiology. A primary therapy for preventing certain SCD complications (e.g., stroke) and for thalassemia major is regular red blood cell (RBC) transfusion, coupled with iron chelation to prevent the complications of transfusion-induced iron overload. For patients with pediatric hematology-oncology diagnoses with chemotherapy-induced aplasia, RBC transfusion is also common, but the degree of transfusion-induced iron overload and its implications for these patients is incompletely understood. Because iron-related tissue toxicity is a major cause of morbidity and mortality in regularly transfused patients, developing strategies to minimize iron loading and iron toxicity is a key objective of this proposal (study Aim #2), stemming from the objective to optimize RBC unit characteristics that patients with SCD and thalassemia receive beyond RBC phenotype matching for Rh C, E and K antigens (study Aim #1). The study will enroll patients with SCD, thalassemia or pediatric oncologic diagnoses receiving eligible transfusion at 6 hospital sites in the United States, as well as patients with SCD at 5 hemocenters in Brazil.

Eligibility criteria: Inclusion Criteria (Aim #1):

* Well-characterized transfusion-dependent form of SCD or thalassemia (including Hemoglobin E-thalassemia and sickle-beta thalassemia) on chronic simple transfusion therapy or partial manual exchange
* On a regular simple RBC transfusion schedule, including partial manual exchange (i.e., 1-3 units scheduled every 2-6 weeks and on a minimum 6-month chronic transfusion trial; for partial manual exchange, the phlebotomy must be completed before the transfusion is started without a back and forth between rounds of phlebotomy and transfusion)
* Seen at any participating domestic hub hospital (i.e., Columbia University Irving Medical Center/Morgan Stanley Children's Hospital of New York, Weill Cornell Medical Center/Komansky Children's Hospital, Boston Children's Hospital, Froedtert \& Medical College of Wisconsin/Children's Wisconsin, University of California San Francisco, Benioff Children's Hospital Oakland) or enrolled in the Brazil REDS-IV-P sickle cell disease cohort and seen at any participating Brazil hemocenter (i.e., Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, HEMOAM - Amazonas, HEMOMINAS - Minas Gerais, HEMOPE -Pernambuco, and HEMORIO - Rio de Janeiro)

Exclusion Criteria (Aim #1):

* Institutionalization or imprisonment
* Foster care
* Weight \<11 kg

Inclusion criteria (Aim #2):

* Either included in Aim #1 (consented patient with SCD or thalassemia) or patient with pediatric oncologic diagnosis under care in a pediatric hematology/oncology service with anemia due to chemotherapy or primary/secondary hypo-proliferative bone marrow requiring a RBC transfusion (including HSCT)
* \[In domestic study only\] Age ≤21 years old (many pediatric services include care of patients up to age 21, therefore the protocol will not limit by age but instead on whether they are seen in a pediatric service)
* Planned transfusion of RBC from an aliquot or unit from a single donor
* Seen at any participating domestic hub hospital (i.e., Columbia University Irving Medical Center/Morgan Stanley Children's Hospital of New York, Weill Cornell Medical Center/Komansky Children's Hospital, Boston Children's Hospital, Froedtert \& Medical College of Wisconsin/Children's Wisconsin, University of California San Francisco, Benioff Children's Hospital Oakland) or at any REDS-IV-P participating Brazil hemocenter (i.e., Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, HEMOAM - Amazonas, HEMOMINAS - Minas Gerais, HEMOPE -Pernambuco, and HEMORIO - Rio de Janeiro).

Exclusion criteria (Aim #2):

* Institutionalization or imprisonment
* Foster care
* Current active auto-immune hemolytic anemia based on positive direct antiglobulin test (DAT) with laboratory evidence of hemolysis and increased transfusion requirement
* \[In domestic study only\] Microangiopathic hemolytic anemia
* Weight \<18 kg

Primary outcomes:
measure: Change in Hemoglobin A or Hemoglobin Level per day (RBC Survival)
timeFrame: Baseline (immediately pre-) to post-transfusion over 2 years
measure: Change in Serum Iron Level
timeFrame: Baseline (immediately before) and 2-hours after transfusion
Secondary outcomes:
measure: Hemoglobin Increment
timeFrame: Baseline (immediately pre-) to post-transfusion, over 2 years
measure: Hemolysis Parameter Increment
timeFrame: Baseline (immediately pre-) to post-transfusion or 2-hours post-transfusion, over 2 years
measure: Hepcidin Level
timeFrame: Baseline (immediately before) to 2 hours after transfusion
measure: Non-Transferrin-Bound Iron (NTBI) Level
timeFrame: Baseline (immediately before) to 2 hours after transfusion
measure: Number of Clinical Complications
timeFrame: 2 years
Other outcomes:
measure: Rate of Alloimmunization
timeFrame: 2 years
measure: 4-hydroxynonenal [4-HNE]
timeFrame: 2 years
measure: Type I interferon (i.e., MxA protein assay) and other cytokines (i.e., IL-6, MCP-1, IFNgamma)
timeFrame: 2 years
measure: Number of Transfusion Reactions
timeFrame: 2 years
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: San Francisco
country: United States
facility: Vitalant Research Institute
state: California
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: New York
country: United States
facility: Weill Cornell Medical Collection (WCMC)/New York Presbyterian Hospital (NYPH)
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center/New York Presbyterian Hospital (NYPH)
state: New York
city: New York
country: United States
facility: New York Blood Center (NYBC)
state: New York
city: Milwaukee
country: United States
facility: Children's Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Versiti Wisconsin, Inc.
state: Wisconsin
city: Manaus
country: Brazil
facility: HEMOAM - Amazonas
state: Amazonas
city: Belo Horizonte
country: Brazil
facility: HEMOMINAS - Minas Gerais
state: Minas Gerais
city: Recife
country: Brazil
facility: HEMOPE - Pernambuco
state: Pernambuco
city: Rio De Janeiro
country: Brazil
facility: HEMORIO - Rio De Janeiro
city: São Paulo
country: Brazil
facility: Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Study officials:
affiliation: Columbia University
name: Eldad A Hod, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vitalant Research Institute
name: Brian Custer, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
References: