Clinical trial NCT05367583: Cohort Study Assessing the Treatment Strategy for High-Risk Myelodysplastic Syndromes in Patients Under 70
Official title: Cohort Study Assessing the Treatment Strategy for High-Risk Myelodysplastic
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Myelodysplastic Syndromes
Keywords: Myelodysplastic syndromes
Allogeneic Stem Cell Transplantation
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2022-05-10
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with MDS-HR defined by an intermediate or high IPSS score (≥ 1.5), or IPSS revised ≥ to 4.5

Brief summary: Myelodysplastic syndromes (MDS) are bone marrow malignant diseases resulting in ineffective haematopoiesis and subsequently, blood cell count decrease. Patients have anaemia responsible of fatigue and high heart frequency, thrombocytopenia responsible of increased risk of bleeding and neutropenia responsible of increased risk of infection. The patients suffering from MDS also are at increased risk of developing acute myeloblastic leukemia (AML). Allogeneic stem cell transplantation (alloSCT) remains the only curative option for patients with aggressive MDS. However, these patients are frequently ineligible for this kind of treatment, because of, for instance, age and co-morbidities. Thus, other treatment options are needed and Azacytidine (AZA), a hypomethylating agent is then proposed. With this COMYRE observatory study, we wanted to analyse which patients undergo alloSCT, why they are not eligible to alloSCT if it is the case, the overall survival of all the patients and if there are some factors which can influence this survival. It could help us to better identify the best candidate for alloSCT and those for other treatments such as AZA.

Detailed description: Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders due to qualitative defects of the hematopoietic stem cell, resulting in uneffective hematopoiesis, dysplasia of one or more lineages, and subsequently, various cytopenias. The patients suffering from MDS are at increased risk of developing acute myeloblastic leukemia (AML). Allogeneic stem cell transplantation (alloSCT) remains the only curative option for patients with intermediate-2 or high risk MDS according to International Prognostic Scoring System (IPSS). However, since these patients are frequently ineligible for this kind of treatment, because of age and co-morbidities, other treatment options were needed. Thank to AZA-001 trial results, Azacytidine (AZA), a hypomethylating agent is validated in Europe for the treatment of MDS patients who are not candidate for alloSCT. In most of cases, AZA is a well-tolerated drug comparing to more classical chemotherapy or alloSCT. Indeed, the most frequent reported side effects are fatigue, constipation, joints and muscle pains, cytopenias and these side effects rarely have significant clinical consequences. On the contrary, during alloSCT procedure, we could observe more infectious events, graft versus host disease, more toxicity.

In this COMYRE observatory study, all high risk MDS with age below 70 are included. The aim of the study is to analyse which patients undergo alloSCT and why they are not eligible to alloSCT if it is the case. We also want to analyse the overall survival of all included patients and we will try to identify if there are some factors which can influence this survival. Thus, it could help us to better identify the best candidate for alloSCT and those for other treatments such as AZA, regarding the benefit/toxicity.

Eligibility criteria: Inclusion Criteria:

* Age\> 18 years old and \<70 years old
* MDS-HR defined by an intermediate or high IPSS score (≥ 1.5), or IPSS revised ≥ to 4.5.
* Diagnosis affirmed by 2 myelograms at least 1 month apart or 1 single characteristic myelogram if prior haematological abnormalities on complete blood count present for more than 6 months
* Free informed consent signed by the patient and the investigator (at the latest on the day of inclusion and before any examination required by the study)
* Affiliate or beneficiary of a social security system

Exclusion Criteria:

* Age ≥ 70 years
* MDS-LR defined by a low IPSS score (\<1.5), or revised IPSS \<4.5
* Women of childbearing potential not using contraception, pregnant or breastfeeding
* Not affiliated to the Social Security system

Primary outcomes:
measure: Proportion of patient treated with Allogeneic stem cell transplantation (alloSCT) among enrolled patients
timeFrame: 3 months from baseline
Secondary outcomes:
measure: Evaluate the feasibility of the alloSCT: Proportion of patients with a donor
timeFrame: 3 months from baseline
measure: Evaluate the effectiveness of iron chelation by measuring plasma ferritin (PF) (PF ≤ 1000 µg/L or PF > 1000 µg/L
timeFrame: Baseline and before alloSCT or 1 year from baseline for patient not treated with alloSCT
measure: Evaluate the overall survival of patient treated and not treated with alloSCT
timeFrame: Until 5 year from baseline
measure: Evaluate overall survival prognostic factors of patient treated and not treated with alloSCT
timeFrame: Baseline
measure: Evaluate response rate to alloSCT or chemotherapy
timeFrame: Until 5 years from baseline
measure: Evaluate toxicity to alloSCT (rate of systemic infection, rate of acute GVHD and rate of chronic GVHD) or chemotherapy (rate of systemic infection and rate of severe hemorrhage)
timeFrame: Until 5 years from baseline
Other outcomes:
Locations:
city: Agen
country: France
facility: CH AGEN
city: Bayonne
country: France
facility: Ch Bayonne
city: Bordeaux
country: France
facility: Chu de Bordeaux
city: Bordeaux
country: France
facility: Institut Bergonie
city: Dax
country: France
facility: CH DAX
city: Libourne
country: France
facility: Ch Libourne
city: Marmande
country: France
facility: Ch Marmande
city: Mont-de-Marsan
country: France
facility: Ch Mont de Marsan
city: Pau
country: France
facility: CH PAU
city: Villeneuve-sur-Lot
country: France
facility: Ch Villeneuve/Lot
Study officials:
References: