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

MDS Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02757989
• Other study ID #: MDS-ALLO-RISK
• Secondary ID: 2015-A00292-47
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 31, 2016
• Est. completion date: June 2024

Study information

• Verified date: February 2024
• Source: Groupe Francophone des Myelodysplasies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 79
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• MDS
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Other:
• transplantation
allogeneic hematopoietic stem cell transplantation in patients with donor

Locations

Country	Name	City	State
France	CHU d'Amiens	Amiens
France	CHU d'Angers	Angers
France	Centre hospitalier Victor Dupouy	Argenteuil
France	CHU Jean Minjoz	Besançon
France	Hôpital Avicenne	Bobigny
France	CHU de Haut Lévèque	Bordeaux
France	CHRU Côte de Nacre	Caen
France	CHU Estaing	Clermont Ferrand
France	CHSF Gilles de Corbeil	Corbeil-Essonnes
France	Hôpital Henri Mondor	Créteil
France	CHU de Grenoble	Grenoble
France	CH Le Mans	Le Mans
France	Hôpital Huriez	Lille
France	Hôpital Saint Vincent de Paul	Lille
France	Hôpital Dupuytren	Limoges
France	Centre hospitalier Lyon Sud	Lyon
France	GHEF, site de Meaux	Meaux
France	CHRU de Montpellier	Montpellier
France	CHU de Nantes	Nantes
France	CHU de Nice	Nice
France	CHU de Nîmes	Nîmes
France	Hôpital Cochin	Paris
France	Hôpital Necker	Paris
France	Hôpital Pitié Salpétrière	Paris
France	Hôpital Saint Louis	Paris
France	CH Joffre	Perpignan
France	CHU de Poitiers	Poitiers
France	CH René Dubos	Pontoise
France	CHU de Reims	Reims
France	Hôpital Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen
France	Institut Curie	Saint-Cloud
France	Institut de cancérologie Lucien Neuwirth	Saint-Priest-en-Jarez
France	Hôpital civil	Strasbourg
France	IUCT-Oncopole	Toulouse
France	Hôpital Bretonneau	Tours
France	Hôpital de Brabois	Vandoeuvre les nancy

Sponsors (3)

Lead Sponsor	Collaborator
Groupe Francophone des Myelodysplasies	Neovii Biotech, Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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