A open label, phase 2, non randomized, multicentre trial to assess the feasibility of induction treatment with 5-azacitidine (5-AZA) followed by allogeneic stem cell transplantation (allo-SCT) or continued 5-AZA treatment in patients without a suitable -sibling or unrelated- stem cell donor with IPSS Int-2/High risk myelodysplastic syndromes (MDS) - BMT-AZA
- Conditions
- myelodysplastic syndrome (MDS)MedDRA version: 9.1Level: LLTClassification code 10028533
- Registration Number
- EUCTR2010-019673-15-IT
- Lead Sponsor
- niversit? Cattolica del Sacro Cuore
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Have a diagnosis of myelodysplastic syndrome (MDS) according to the WHO classification for MDS (Appendix F) with a intermediate-2 or high IPSS score (score = 1.5, Appendix G) or a diagnosis of CMMoL according to the FAB classification (appendix B) with 10-20% BM or PB blasts and WBC < 20 x 109/L (preliminary cytoreduction using hydroxyurea is allowed); • Age =18 to 65 years; • Potential candidates for HSCT • life expectancy =3 months; • Signed written informed consent according to IGH/EU/GCP and national local laws; • Eastern Cooperative Oncology Group Performance Status Grade of 0-2 (Appendix I); • Serum bilirubin levels =1.5 x the upper limit of the normal (ULN) range for the laboratory; higher levels are acceptable if these can be attributed to active hemolysis (as indicated by positive direct Coombs’ testing, decreased haptoglobin level, elevated indirect bilirubin and/or lactate dehydrogenase), or ineffective erythropoiesis (as indicated by bone marrow findings). The decision of including these patients into the study will be under the responsibility of the study chairman (waiver for enrollment). • Serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) or serum glutamic-pyruvic transaminase (alanine aminotransferase) levels =2 x ULN; • Women of childbearing potential may participate, providing they meet the following conditions: - Must not start a pregnancy throughout the study and for 6 months following the date of the last dose of study medications; - Must have a negative serum pregnancy test obtained within 48 hours prior to Day 1. • Males with female partner of childbearing potential must avoid fathering throughout the study and for 6 months following the date of the last dose of study medication.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
-acute myeloid leukaemia;
-concurrent malignancy diagnosed in the past 12 months (with the exception of skin basalioma);
-severe renal impairment (creatinine clearance <30 ml/min);
-severe congestive heart failure (EF =50% ) or unstable cardiac disease (NYHA 3-4);
-severe pulmonary disease (DLCO and/or FEV1 =65% or dyspnea at rest or requiring oxygen);
-pregnant or lactating or potentially fertile (both males and females), who have not agreed to avoid pregnancy during the trial period;
-liver disease characterized by AST and ALT level >2 x ULN and total bilirubin >1.5 x ULN (unless due to active hemolysis or ineffective erythropoiesis;
-HIV infection;
-active, uncontrolled HCV or HBV infections or liver cirrhosis;
-clinically relevant neurological diseases;
-psychiatric illness that would prevent granting of informed consent;
-hypersensitivity (known or suspected) to Azacitidine or Mannitol;
-prior Treatments: Prior investigational drugs (within 30 days)
Radiotherapy, chemotherapy, or cytotoxic therapy for non-MDS conditions within the previous 6 months
Growth factors (EPO, G-CSF or GM-CSF) during the previous 21 days
Androgenic hormones during the previous 14 days
Prior transplantation or cytotoxic therapy, including azacitidine and chemotherapy, administered to treat MDS.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the feasibility of allo-BMT after 5-azacitidine as first line therapy before allotransplant.;Primary end point(s): • the rate of enrolled patients suitable to BMT and currently performing BMT after 5-azacitidine.;Secondary Objective: • Efficacy and safety of 5-AZA in patients not receiving HSCT for any reasons • Overall response rate (ORR) to 5-azacitidine • Overall Survival (OS) at 1 year • Disease Free Survival (DFS) at 1 year • Transplant related Mortality (TRM) at 1 year after transplantation • Time to progression of MDS • Time to progression to AML • Rate of hematopoietic engraftment
- Secondary Outcome Measures
Name Time Method