Clinical trial NCT03643042: Impact of 2 Transfusion Strategies on Quality of Life of Multitransfused Patients With Low-risk Myelodysplastic Syndrome
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Myelodysplastic Syndromes
Transfusion-dependent Anemia
Keywords: Myelodysplastic Syndromes
Transfusion
Quality of life
Physical performance
Lead sponsor: Lille Catholic University
Sponsor class: OTHER
First posted: 2018-08-22
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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/L
Primary purpose: PREVENTION

Brief summary: Myelodysplastic syndromes (MDS) are heterogeneous malignant bone marrow disorders characterized by ineffective haematopoiesis, peripheral blood cytopenias and variable risk of leukaemia transformation.

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

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

Eligibility criteria: 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

Primary outcomes:
measure: Quality of Life by Myelodysplasia Scale (QUALMS) score
timeFrame: six months post-randomization
Secondary outcomes:
measure: Quality of Life by Myelodysplasia Scale (QUALMS) score over the twelve months of follow-up
timeFrame: 3, 6, 12 Months
measure: Timed up and go test over the twelve months of follow-up
timeFrame: 3, 6, 12 Months
measure: Transfusion incidents rate over the twelve months of follow-up
timeFrame: 3, 6, 12 Months
measure: Transfusion costs over the twelve months of follow-up
timeFrame: 3, 6, 12 Months
measure: Time of occurrence of diagnosis of heart and liver damage due to transfusional iron overload over twelve months of follow-up
timeFrame: 3, 6, 12 Months
Other outcomes:
Locations:
city: Abbeville
country: France
facility: Abbeville CH
city: Amiens
country: France
facility: Amiens CHU
city: Arras
country: France
facility: Arras CH
city: Avignon
country: France
facility: Henri Duffaut CH
city: Besançon
country: France
facility: Besançon CHU
city: Bordeaux
country: France
facility: Bordeaux CHU
city: Caen
country: France
facility: Cote de Nacre CHU
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand CHU
city: Dunkerque
country: France
facility: Dunkerque CH
city: Grenoble
country: France
facility: Grenoble CHU
city: Le Mans
country: France
facility: Le Mans CH
city: Lens
country: France
facility: Lens CH
city: Lille
country: France
facility: St-Vincent Hospital
city: Limoges
country: France
facility: Limoges CHRU
city: Meaux
country: France
facility: Meaux CH
city: Nice
country: France
facility: Archet 1 Hospital
city: Paris
country: France
facility: Saint-Louis Hospital, APHP
city: Rennes
country: France
facility: Pontchaillou Hospital
city: Roubaix
country: France
facility: Roubaix CH
Study officials:
affiliation: GHICL
name: Laurent Pascal, MD
role: STUDY_DIRECTOR
References: