Red Blood Cell Transfusion Thresholds and QOL in MDS

Quality of Life Clinical Trial

— EnhanceRBC  

Official title:

Red Blood Cell Transfusion Thresholds and QOL in MDS (EnhanceRBC): a Pilot, Feasibility Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02099669
• Other study ID #: OCCMDS-005
• Status: Recruiting
• Phase: N/A
• First received: March 26, 2014
• Last updated: April 24, 2018
• Start date: March 2014
• Est. completion date: January 2019

Study information

• Verified date: April 2018
• Source: Sunnybrook Health Sciences Centre
• Contact: Jennifer Gallagher
• Email: jennifer.gallagher[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Myelodysplastic syndromes (MDS) are bone marrow malignancies characterized by poor bone marrow function that may progress to acute myeloid leukemia. Many patients become red blood cell transfusion-dependent. Transfusion dependence is associated with inferior quality of life (QOL). However, the relationship between the degree of anemia and QOL is less clear. A commonly used transfusion strategy is to target the hemoglobin (Hb) in the range of 80-90 g/L (normal hemoglobin > 120-130g/L). The question is: would a higher hemoglobin target lead to improvement in QOL despite the negative impact transfusion dependence may have on QOL (due to associated time commitments, expense, transfusion reactions etc). Several groups have prospectively shown that targeting hemoglobin levels of greater than 120 g/L (with hematopoietic growth factors (HGFs) and/or blood transfusions) or incremental increases of 15-20 g/L (with HGFs alone) were associated with improved QOL. The investigators MDS program has been conducting prospective assessments of QOL since 2007 in all registered and consented patients using a variety of validated questionnaires. Preliminary analysis (in 236 patients) revealed that, compared with an age-matched healthy general population, MDS patients have inferior QOL. Transfusion dependence and anemia were independently predictive of poor functioning, fatigue and decreased health utility. Furthermore, a hemoglobin level of ≥100 g/L seemed to be the key threshold for improvement in function and symptom scores. The investigators hypothesize that the target hemoglobins in transfusion dependent MDS patients are too low and this may account for their inferior quality of life. Our goal is to compare the effect on QOL of a restrictive strategy (which is the current standard of care), with a liberal transfusion strategy in a large randomized controlled trial of transfusion dependent MDS outpatients. Before embarking on such an endeavor, the investigators must first prove feasibility in a smaller pilot randomized controlled trial.

Description:

Myelodysplastic syndromes (MDS) are bone marrow malignancies characterized by poor bone marrow function that may progress to acute myeloid leukemia. Many patients become red blood cell transfusion-dependent. Transfusion dependence is associated with inferior quality of life (QOL). However, the relationship between the degree of anemia and QOL is less clear. A commonly used transfusion strategy is to target the hemoglobin (Hb) in the range of 80-90 g/L (normal hemoglobin > 120-130g/L). The question is: would a higher hemoglobin target lead to improvement in QOL despite the negative impact transfusion dependence may have on QOL (due to associated time commitments, expense, transfusion reactions etc). Several groups have prospectively shown that targeting hemoglobin levels of greater than 120 g/L (with hematopoietic growth factors (HGFs) and/or blood transfusions) or incremental increases of 15-20 g/L (with HGFs alone) were associated with improved QOL. The investigators MDS program has been conducting prospective assessments of QOL since 2007 in all registered and consented patients using a variety of validated questionnaires. Preliminary analysis (in 236 patients) revealed that, compared with an age-matched healthy general population, MDS patients have inferior QOL. Transfusion dependence and anemia were independently predictive of poor functioning, fatigue and decreased health utility. Furthermore, a hemoglobin level of ≥100 g/L seemed to be the key threshold for improvement in function and symptom scores. The investigators hypothesize that the target hemoglobins in transfusion dependent MDS patients are too low and this may account for their inferior quality of life. Our goal is to compare the effect on QOL of a restrictive strategy (which is the current standard of care), with a liberal transfusion strategy in a large randomized controlled trial of transfusion dependent MDS outpatients. Before embarking on such an endeavor, the investigators must first prove feasibility in a smaller pilot randomized controlled trial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients with MDS =18 years of age

• Transfusion dependent: at least 1 transfusion per month in the last 8 weeks

• Hb <100g/L pre transfusion

• Life expectancy > 6 months

Exclusion Criteria:

• Unstable cardiac disease (Canadian Cardiovascular Society (CCS) III/IV angina or New York Heart Association (NYHA) III/IV congestive heart failure) requiring the transfusion target range to remain >85-100 g/L at all times

• ECOG =3

• Patients with red cell antibodies against high frequency antigens or multiple antibodies (would potentially delay finding blood)

• Patients on ESA's or disease modifying agents (like azacitidine) for their MDS

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Myelodysplastic Syndromes (MDS)
• Preleukemia
• Quality of Life
• Red Blood Cell (RBC) Transfusions

Intervention

Other:
• Red Blood Cell Transfusions

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Princess Margaret Hospital	Toronto
Canada	Sunnybrook Health Sciences Centre/Odette Cancer Centre	Toronto

Sponsors (3)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Juravinski Cancer Center, Princess Margaret Hospital, Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage compliance of q2weekly hemoglobins	The percentage compliance of q2weekly hemoglobins being within or above the target range of the RBC transfusion threshold assigned (after the 4 week run-in at study start as defined above). We will consider this study feasible and worthy of future development into a larger randomized trial (powered for QOL difference) if compliance is =70%. A compliance rate of 50-70%, would not exclude going forward with such an RCT but only after careful discussion and statistical planning	3 months
Secondary	Measures of feasibility	Number of patients ineligible due to screen failure; Enrolment rates defined by the number of enrolled patients/month; Percentage compliance with QOL questionnaire completion at least 3 serial times; Other logistical issues related to protocol implementation, recruitment rates, randomization implementation strategy, data collection, patient tolerability of study schedule	3 months
Secondary	Quality of life	• The magnitude of change in physical functioning, fatigue, dyspnea and global health scores on the EORTC QLQ-C30, calculated health utility on the EQ-5D and fatigue score on FACT-F comparing the 2 RBC transfusion thresholds above.	3 months
Secondary	Adverse events	The rate of transfusion reactions (as defined by TTISS (Transfusion Transmitted Injuries Surveillance System by Public Health Agency of Canada)); Rate of adverse events such as cardiac events and thromboembolic events as per NCI CTCAE version 4.0 criteria	3 months
Secondary	Alloimmunization rates	Rate of alloimmunization to significant blood group antigens	3 months
Secondary	Hemosiderosis	• The impact on transfusion associated hemosiderosis rates and burdens (as measured by changes in ferritin levels and iron chelating medications)	3 months
Secondary	Overall utilization of blood	How many units of blood are required to maintain the hemoglobin threshold chosen	3 months
Secondary	Time commitment	• The overall time commitment per group, measured as the time spent in transfusion medicine clinic	3 months