Azacytidine and Lymphocytes in Relapse of AML or MDS After Allogeneic Stem Cell Transplantation.
Acute Myelogenous Leukemia, Myelodysplastic Syndrome
About this trial
This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring Hematology, Acute Myelogenous Leukemia, Myelodysplasic syndrome, Allogeneic stem cell transplantation, Donor lymphocyte infusion, DLI, Azacytidine, Vidaza, Overall response rate, Relapse
Eligibility Criteria
Inclusion Criteria:
Patients:
- Age ≥ 18 years
- Be able to understand and sign informed consent
- Fertile patients must use a reliable contraception method
Disease status at transplantation:
- AML in first or subsequent complete remission (< 5% marrow blasts)
- MDS with less than 10% marrow blasts at the time of transplantation
Transplantation:
- Allogeneic transplantation using a sibling or unrelated donor with matching in 10/10 alleles (HLA-A, B, C, DRB1, DQB1) or maximum of one allele or one antigen or 1 antigen + 1 allele or 1 antigen + 1 DQB1 antigen or 2 alleles mismatches.
- Myeloablative or reduced-intensity conditioning
- Second transplantation is allowed
- Donor is willing to donate lymphocytes
Clinical situation:
- Cytological relapse after allo-SCT defined as the recurrence of more than 5% blasts on bone marrow aspiration (AML) or evidence of MDS
- Immunophenotypic relapse defined as the recurrence of an abnormal phenotype on flow cytometry in bone marrow aspirate (only in case of a specific phenotype).
- Cytogenetic or molecular relapse defined as the persistence or recurrence of a cytogenetic abnormality or molecular marker in bone marrow aspiration or peripheral blood. WT1 expression is not considered as reliable marker for relapse in this protocol but FLT3-ITD, NPM1, CEBPA, or translocation-specific markers (such as MLL-PTD, AML-ETO, CBFB-MYH11) are.
- Immunosuppressive therapy should have been stopped before inclusion.
Exclusion Criteria:
- More than 30% marrow blasts at the time of inclusion
- Extramedullary relapse including CNS involvement
- ECOG Performance status > 2
- Active acute grade II-IV GvHD at the time of inclusion
- Active chronic GvHD requiring systemic therapy at the time of inclusion
- Uncontrolled infection
- HIV positive
- Acute or chronic heart failure (NYHA class III or IV) or symptomatic ischemic heart disease or ejection fraction < 35% or uncontrolled arrhythmia
- Severe liver failure (total bilirubin > 3 mg/dL, SGPT > 4 X upper normal limit)
- Severe pulmonary failure (corrected DLCo < 35%)
- Terminal renal failure requiring dialysis
- Severe neurological or psychiatric disorders
- Concurrent investigational drug.
- Other treatment for relapse, except for hydroxyurea but it should be stopped before inclusion in the study.
- Female who is pregnant or breastfeeding
Sites / Locations
- Ziekenhuis Netwerk Antwerpen
- AZ Sint-Jan Brugge
- Institut Jules Bordet
- Universitair Ziekenhuis Antwerpen
- Universitair Ziekenhuis Gent
- Hopital de Jolimont
- Universitair Ziekenhuis Brussel
- Universitair Ziekenhuis Leuven
- CHU Liège
- Hartziekenhuis Roeselare Menen
- Cliniques Universitaires Saint-Luc
- CHU Mont-Godinne
Arms of the Study
Arm 1
Experimental
Azacytidine + Donor lymphocyte infusion
Azacytidine will be administered subcutaneously for 5 days. During the first cycle, a dose of 100mg/m2/day will be used and for the following cycles a dose of 35mg/m2/day will be administered. Each cycle will consist in 28 days. All patients will receive at least 6 cycles of Azacytidine and the total number of cycles will depend on the response to treatment. Donor lymphocyte infusion will be performed on day 1 of cycle 2, 4 and 6 of Azacytidine. The amount of cells infused will depend on donor origin.