SMD-transfu: Impact of 2 Transfusion Strategies on Quality of Life of Multitransfused Patients With Low-risk Myelodysplastic Syndrome

Sponsor

Lille Catholic University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03643042

Collaborator

(none)

174

Enrollment

Locations

Arms

49.2

Anticipated Duration (Months)

9.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Anemia is the most common manifestation of bone marrow failure in MDS. After failure with first-line treatment by Erythropoietin, patients survive in average 5 years under long term blood transfusion. Modalities of blood transfusion are not clearly defined.

Then, the objective of this randomized comparative multicentric study is to compare two modalities of threshold for transfusion:

Restrictive group: Hb < 80g/L and Hb maintain between 80 and 100g/L
Liberal group: Hb < 100g/L and Hb maintain between 100 and 120g/L

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes Transfusion-dependent Anemia	Other: Transfusion	N/A

Detailed Description

Myelodysplastic syndromes (MDS) are heterogeneous malignant bone marrow disorders characterized by ineffective haematopoiesis, peripheral blood cytopenias and variable risk of leukaemia transformation. The median age at diagnosis is 75 years. The incidence is about 30 per 100,000, over 70 years. Etiology is unknown in more than 85% of cases, chemo-induced causes and family cases are well individualized.

Diagnosis, prognosis, and classification (WHO) are based on joint cytologic analysis of peripheral blood, bone marrow, and spinal cytogenetic analysis. The main therapeutic objectives in low-risk MDS are to correct cytopenias, improve quality of life and prevent aggravation of co-morbidities.

Anemia is the most common manifestation of bone marrow failure in MDS. It is encountered in 80% of cases at diagnosis and almost always occurs in the progression of the disease. Its presence and importance have a pejorative prognostic value, but it is not clear whether this anemia is indicative of a more serious clonal disease or whether it is the repercussions of anemia that lead to a more severe prognosis. After failure with first-line treatment by Erythropoietin (EPO), patients survive in average 5 years under long term blood transfusion. Modalities of blood transfusion are not clearly defined.

Studies in the general geriatric population and in cases of acute anemia are in favor of a restrictive transfusion regimen (threshold around 70 g/L), while experience during MDS with EPO suggest that maintaining a higher hemoglobin count could have a favorable impact on quality of life, physical performance, or even survival of patients with MDS.

Then, the objective of this randomized comparative multicentric study is to compare two modalities of threshold for transfusion:

Restrictive group: Hb < 80g/L and Hb maintain between 80 and 100g/L
Liberal group: Hb < 100g/L and Hb maintain between 100 and 120g/L

Study Design

Study Type:

Interventional

Anticipated Enrollment :

174 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Two modalities of threshold for transfusion: Restrictive group: Hb < 80g/L and Hb maintain between 80 and 100g/L Liberal group: Hb < 100g/L and Hb maintain between 100 and 120g/LTwo modalities of threshold for transfusion:Restrictive group: Hb < 80g/L and Hb maintain between 80 and 100g/L Liberal group: Hb < 100g/L and Hb maintain between 100 and 120g/L

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Impact of 2 Transfusion Strategies on the Quality of Life of Multi-transfused Patients With Low Risk Myelodysplastic Syndrome: Multicenter Randomized Trial Comparing a Liberal vs. Restrictive Transfusion Regimen

Actual Study Start Date :

Mar 24, 2021

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Restrictive group Transfusion with: Hb < 80g/L and Hb maintain between 80 and 100g/L	Other: Transfusion Transfusion with Hb maintain between 80 and 100g/L or Hb maintain between 100 and 120g/L
Experimental: Liberal group Transfusion with: Hb < 100g/L and Hb maintain between 100 and 120g/L	Other: Transfusion Transfusion with Hb maintain between 80 and 100g/L or Hb maintain between 100 and 120g/L

Arm

Intervention/Treatment

Experimental: Restrictive group

Transfusion with: Hb < 80g/L and Hb maintain between 80 and 100g/L

Other: Transfusion

Transfusion with Hb maintain between 80 and 100g/L or Hb maintain between 100 and 120g/L

Experimental: Liberal group

Transfusion with: Hb < 100g/L and Hb maintain between 100 and 120g/L

Other: Transfusion

Transfusion with Hb maintain between 80 and 100g/L or Hb maintain between 100 and 120g/L

Outcome Measures

Primary Outcome Measures

Quality of Life by Myelodysplasia Scale (QUALMS) score [six months post-randomization]
Quality of Life assessed by a specific validated and adapted disease scale :Quality of Life by Myelodysplasia Scale (QUALMS) score at six months post-randomization. The QUALMS consists of 38 items, and takes less than 10 minutes to complete. Scored on a scale of 0 to 100 higher score is correlated with better MDS-specific quality of life.

Secondary Outcome Measures

Quality of Life by Myelodysplasia Scale (QUALMS) score over the twelve months of follow-up [3, 6, 12 Months]
Evolution of the QUALMS score over the twelve months of follow-up. Scored on a scale of 0 to 100 higher score is correlated with better MDS-specific quality of life.
Timed up and go test over the twelve months of follow-up [3, 6, 12 Months]
Evolution of physical performance (the time required for the Timed up and go test) at six months post-randomization and over the twelve months of follow-up
Transfusion incidents rate over the twelve months of follow-up [3, 6, 12 Months]
Transfusion incidents rate during the twelve months of follow-up among allo-immunization, hospitalization for pulmonary overload, iron overload (ferritin, transferrin saturation), TRALI (Transfusion-Related Acute Lung Injury)
Transfusion costs over the twelve months of follow-up [3, 6, 12 Months]
Transfusion costs (number of Packed red blood cells (PRBC) used) during the twelve months of follow-up
Time of occurrence of diagnosis of heart and liver damage due to transfusional iron overload over twelve months of follow-up [3, 6, 12 Months]
Time of occurrence of diagnosis of heart and liver damage due to transfusional iron overload over twelve months of follow-up. The diagnosis will be established according to the standard procedure based on annual MRI, in particular by measuring the LIC (liver iron concentration), the MIC (myocardial iron concentration) and the cardiac T2* value.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with low risk or intermediate risk MDS: Revised International Prognostic Scoring System (IPSS-R) less than or equal to 4.5
Relapse or failure after Erythropoiesis-Stimulating Agent (ESA) therapy or others treatments (Lenalidomide, Thalidomide, 5-Azacytidine, antithymocyte globulin (ATG), Luspatercept, Decitabine, allograft)
Transfusion dependent: in average at least 3 transfusion episodes in the last 6 months and total of packed red blood cells (PRBC): more than 8 in the last 12 months and less than 150 in total.
≥ 18 years of age
The Eastern Cooperative Oncology Group (ECOG) score < 4
Life expectancy > 12 Months
Patients willing to participate in the study and who have signed the informed consent form

Exclusion Criteria:

Patients with disease modifying agents for their MDS such as: ESA therapy, Lenalidomide, Thalidomide revlimid, Vidaza, Allograft, antithymocyte globulin (ATG), Luspatercept, Decitabine, experimental agents, other clinical trial, taken within 3 months prior to inclusion (chelators are accepted)
According to physician: unable to tolerate restrictive or liberal red cell transfusion thresholds (e.g. clinically significant cardio-respiratory failure)
Cognitive alteration (inability to complete QUALMS)
Inability to perform the physical performance test Timed up and go test
Splenomegaly > 3 cm below the costal margin
Severe renal failure with creatinine clearance < 30ml / min
Patients presenting with active bleeding or evidence of significant haemolysis
Patient under guardianship or curatorship

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Abbeville CH	Abbeville	France	80142
2	Amiens CHU	Amiens	France	80054
3	Arras CH	Arras	France	62000
4	Henri Duffaut CH	Avignon	France	84000
5	Besançon CHU	Besançon	France	25030
6	Bordeaux CHU	Bordeaux	France	33604
7	Cote de Nacre CHU	Caen	France	14033
8	Clermont-Ferrand CHU	Clermont-Ferrand	France	63000
9	Dunkerque CH	Dunkerque	France	59140
10	Grenoble CHU	Grenoble	France	38043
11	Le Mans CH	Le Mans	France	72037
12	Lens CH	Lens	France	62307
13	St-Vincent Hospital	Lille	France	59020
14	Limoges CHRU	Limoges	France	87042
15	Meaux CH	Meaux	France	77104
16	Archet 1 Hospital	Nice	France	06202
17	Saint-Louis Hospital, APHP	Paris	France	75475
18	Pontchaillou Hospital	Rennes	France	35033
19	Roubaix CH	Roubaix	France	59100