VIDAZA-DLI Pre-emptive Azacitidine and Donor Lymphocyte Infusions Following Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome (VIDAZA-DLI)
|Acute Myeloid Leukemia Myelodysplastic Syndrome||Drug: Azacitidine Other: DLI||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pre-emptive Azacitidine and Donor Lymphocyte Infusions Following Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome|
- Evaluation of the cumulative incidence of relapse rate [ Time Frame: 2 years ]An A'Hern procedure will be used (cf. 11.1): If the number of patients not relapsed at two year will be 18 or more out of 24 patients, the null hypothesis will be rejected and the relapse rate will be considered acceptable.
- Evaluation of disease-free survival (DFS) at 2 years from transplantation [ Time Frame: 2 years ]Kaplan-Meier method
- Measure the overall survival rate at 2 years [ Time Frame: 2 years ]Kaplan-Meier method
- Cumulative incidence death from leukemia, and non relapse mortality (NRM) [ Time Frame: 2 years ]cumulative incidence function for disease free survival at 2 years from transplantation, GVHD, death from leukaemia and non-relapse mortality will be estimated (patients are at risk not only for relapse but can also be "removed" from possible relapse because of competing events such as death in remission (due to infection or GVHD)).
- Feasibility and safety of administrating maintenance azacitidine following allogenic transplantaton [ Time Frame: 2 years ]To evaluate toxicity induced by the azacitidine and DLI, different parameters will be studied:Cell Blood Count with differential, liver function tests, serum creatinine, BUN and total protein will be performed weekly from the time of initiation of azacitidine administration until completion of the last DLI. Performance Status,Acute GVHD,Bone marrow aspiration with evaluation of morphological response as well as chimerism from peripheral blood will be performed prior starting azacitidine, following 3 cycles of azacitidine and after the seventh cycle and twelfth cycle of azacitidine.
- Feasibility and safety of performing prophylactic donor lymphocytes infusion [ Time Frame: 2 years ]
The relatedness of observed toxicity to DLI will be evaluated and documented:
- Maximum toxicity with respect to mucositis, liver, kidney, lung, heart, neurological system according to CTC criteria (cf. appendices).
- Infections (bacteremia, fungemia, invasive fungal infection, CMV reactivation and disease, other viral reactivation or infection).
- Grade of acute and chronic GVHD (cf. appendices); GVHD is classified according to clinical symptoms, irrespective to the time interval to DLI.
- Bone marrow aspiration, as well as chimerism in PB.
- Incidence and severity of acute and chronic graft-versus-host disease [ Time Frame: 2 years ]
Symptoms related to GVHD should be reported within the GVHD section of the case reporting files. AE and SAE are documented in the patient's chart
- on a daily basis, as long as the patient is on ward, and
- on a weekly to two-monthly basis during outpatient follow up, depending on the frequency of outpatient visits on the respective patient.
|Study Start Date:||November 2011|
|Study Completion Date:||July 2015|
|Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Donor lymphocyte infusion (DLI) is to be given from day +126 (week 18) in patients without immunosuppressive therapy for at least one month and following 3 cycles of AZA, and without clinical signs of GVHD, and without uncontrolled infection and without a recent history of >grade 2 acute GVHD. DLI are schedules every 8 weeks. There are 3 DLI scheduled.
If first cycle of AZA is postponed beyond day 56 (maximum to Day 100), all subsequent cycles and DLI will be post poned too.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01541280
|University Hospital of Nantes|
|Nantes, France, 44000|
|Principal Investigator:||Milpied Noel, Professor||CHU BORDEAUX|
|Principal Investigator:||Guillaume Thierry, Doctor||CHU Nantes|
|Principal Investigator:||Yakoub-Agha Ibrahim, Professor||CHU Lille|
|Principal Investigator:||Huynh Anne, Doctor||CHU Toulouse|
|Principal Investigator:||Blaise Didier, Professor||Institut-Paoli Calmettes Marseille|
|Principal Investigator:||Mohamad Mothy, Professor||Hôpital Saint Antoine|