Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Myelodysplastic Syndrome Low Risk

Study Overview
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Brief Summary
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Comparison of survival in patients with or without a matched donor at 36 months

Detailed Description
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Patients with a matched donor (8/8 at molecular level unrelated donor or matched sibling) received an allogeneic hematopoietic stem cell transplantation. Patients without a matched donor received the best available treatment. All patients will be followed at least 36 months or until the end of the study.

Official Title
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Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Low or Intermediate-1 Myelodysplastic Syndrome: A Prospective Multicenter Phase II Study Based on Donor Availability on Behalf of the GFM & SFGM-TC

Conditions
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MDS

Intervention / Treatment
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* Other: transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed consent Classical IPSS intermediate 1 or low myelodysplastic syndrome associated with at least one poor prognosis feature: Intermediate or higher risk revised IPSS RBC transfusion dependent anemia and failure to 2 or more lines or therapy (including EPO, Lenalidomide or demethylating agent…) thrombocytopenia < 20 G/L requiring transfusion neutropenia < 0.5 G/L associated with severe infection (defined as requiring hospitalization) Patient aged ≥ 18 and < 70 years For young patients, 18-45 years, Fanconi disease and dyskeratosis should be ruled out Patient for whom a transplantation from a matched donor, (8/8 (HLA A, B, C, DRB1) identical at molecular level)unrelated donor or matched sibling), is considered irrespective of donor availability Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale (At time of screening) Negative pregnancy and adequate contraception (including in male patients wishing to father), if relevant. Wash-out of at least 30 days since a previous treatment with Vidaza, Lenalidomide, EPO or any other treatment inducing cytopenias. Exclusion Criteria: MDS classified according to classical IPSS as intermediate 2 or High risk Transformation in Acute myeloid Leukemia (AML) Severe active infection or any other uncontrolled severe condition. Organ dysfunctions including the following Hepatic : total bilirubin > 2 times upper limit of normal (ULN) (except moderate unconjugated hyperbilirubinemia due to intra medullary hemolysis or Gilbert syndrome) , alanine transaminase (ALT) and aspartate transaminase (AST) > 3xULN Symptomatic respiratory chronic failure Symptomatic cardiac failure Renal clearance < 60ml/min Prior malignancy (except in situ cervix carcinoma, limited basal cell carcinoma, or other tumors if not active during the last 3 years) MDS with the following causal germline disease : Fanconi anemia, GATA2 related syndromes and telomere disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with donor<br>Patients with a matched donor (8/8 at molecular level unrelated donor or matched sibling) | Other: transplantation<br>* allogeneic hematopoietic stem cell transplantation in patients with donor<br>|
| No Intervention: Patients without donor<br>Patients without a matched donor | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | comparison of overall survival in patients with or without a matched donor (8/8 unrelated donor or matched sibling) at 36 months | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life | comparison of quality of life in patients with or without a matched donor, quality of life assessed by questionnaire (EORTC version 3) at inclusion, 12, 24 and 36 months | 12, 24 and 36 months | 
| number of patients with complete response at 36 month | comparison between patients with or without a donor for cumulative incidence of complete response at 36 month | 36 months | 
| number of patients with transformation in AML at 36 month | comparison between patients with or without a donor for cumulative incidence of transformation in AML at 36 month | 36 months | 
| proportion of patients with iron overload | proportion of patients with iron overload (Serum Ferritin (SF)>1000 ng/mL or Red Blood Cells transfusion>20) at time of inclusion and at 16 month after inclusion for non-transplanted patients and 12 months post-transplant for transplanted patients | 16 months | 
| evolution of innovative iron markers including Non-transferrin binding iron (NTBI), labile plasmatic Iron (LPI) and Hepcidine | evolution of innovative iron markers including Non-transferrin binding iron (NTBI), labile plasmatic Iron (LPI) and Hepcidine measured at time of inclusion, at 3 month and 16 month post-inclusion for all patients; In transplanted patients these markers will be measured just before conditioning regimen (J-5), Just before the transplantation (J0), at D7, 30, 100 and 12 month after transplant. | 3 and 16 months | 
| efficiency of chelation | the effect of chelation will be assessed at 3 month after inclusion for all patient and post transplant by measuring Serum ferritin level | 3 and 16 months | 
| number of patients with adverse events grade III and IV as assessed by CTCAE v4.0 | comparison between patients with or without a donor for number of Grade III and IV toxicities (hematological and non-hematological) recorded according to NCI CTCAE criteria versions 4.0 during the 36 months | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low risk MDS, Transplantation