Clinical trial NCT02757989: Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Myelodysplastic Syndrome Low Risk
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: MDS
Keywords: Low risk MDS
Transplantation
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
Collaborators: name: Novartis
name: Neovii Biotech
First posted: 2016-05-02
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Comparison of survival in patients with or without a matched donor at 36 months

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Signed Informed consent
2. Classical IPSS intermediate 1 or low myelodysplastic syndrome associated with at least one poor prognosis feature:

   1. Intermediate or higher risk revised IPSS
   2. RBC transfusion dependent anemia and failure to 2 or more lines or therapy (including EPO, Lenalidomide or demethylating agent...)
   3. thrombocytopenia \< 20 G/L requiring transfusion
   4. neutropenia \< 0.5 G/L associated with severe infection (defined as requiring hospitalization)
3. Patient aged ≥ 18 and \< 70 years For young patients, 18-45 years, Fanconi disease and dyskeratosis should be ruled out
4. 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
5. Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale (At time of screening)
6. Negative pregnancy and adequate contraception (including in male patients wishing to father), if relevant.
7. Wash-out of at least 30 days since a previous treatment with Vidaza, Lenalidomide, EPO or any other treatment inducing cytopenias.

Exclusion Criteria:

1. MDS classified according to classical IPSS as intermediate 2 or High risk
2. Transformation in Acute myeloid Leukemia (AML)
3. Severe active infection or any other uncontrolled severe condition.
4. 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
5. Prior malignancy (except in situ cervix carcinoma, limited basal cell carcinoma, or other tumors if not active during the last 3 years)
6. MDS with the following causal germline disease : Fanconi anemia, GATA2 related syndromes and telomere disorders

Primary outcomes:
measure: overall survival
timeFrame: 36 months
Secondary outcomes:
measure: quality of life
timeFrame: 12, 24 and 36 months
measure: number of patients with complete response at 36 month
timeFrame: 36 months
measure: number of patients with transformation in AML at 36 month
timeFrame: 36 months
measure: proportion of patients with iron overload
timeFrame: 16 months
measure: evolution of innovative iron markers including Non-transferrin binding iron (NTBI), labile plasmatic Iron (LPI) and Hepcidine
timeFrame: 3 and 16 months
measure: efficiency of chelation
timeFrame: 3 and 16 months
measure: number of patients with adverse events grade III and IV as assessed by CTCAE v4.0
timeFrame: 36 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU d'Angers
city: Argenteuil
country: France
facility: Centre hospitalier Victor Dupouy
city: Besançon
country: France
facility: CHU Jean Minjoz
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: CHU de Haut Lévèque
city: Caen
country: France
facility: CHRU Côte de Nacre
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Corbeil-Essonnes
country: France
facility: CHSF Gilles de Corbeil
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Grenoble
country: France
facility: CHU de Grenoble
city: Le Mans
country: France
facility: CH Le Mans
city: Lille
country: France
facility: Hôpital Saint Vincent de Paul
city: Lille
country: France
facility: Hôpital Huriez
city: Limoges
country: France
facility: Hôpital Dupuytren
city: Lyon
country: France
facility: Centre hospitalier Lyon Sud
city: Meaux
country: France
facility: GHEF, site de Meaux
city: Montpellier
country: France
facility: CHRU de Montpellier
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: CHU de Nice
city: Nîmes
country: France
facility: CHU de Nîmes
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Pitié Salpétrière
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Necker
city: Perpignan
country: France
facility: CH Joffre
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pontoise
country: France
facility: CH René Dubos
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Cloud
country: France
facility: Institut Curie
city: Saint-Priest-en-Jarez
country: France
facility: Institut de cancérologie Lucien Neuwirth
city: Strasbourg
country: France
facility: Hôpital civil
city: Toulouse
country: France
facility: IUCT-Oncopole
city: Tours
country: France
facility: Hôpital Bretonneau
city: Vandoeuvre les nancy
country: France
facility: Hôpital de Brabois
Study officials:
affiliation: Saint-Louis Hospital, Paris, France
name: Marie Robin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Robin M, Fenaux P. Which lower risk myelodysplastic syndromes should be treated with allogeneic hematopoietic stem cell transplantation? Leukemia. 2020 Oct;34(10):2552-2560. doi: 10.1038/s41375-020-0967-x. Epub 2020 Jul 13.