This open label phase-II trial evaluates hematological response of an additional treatment with 5-Azacitidine to common DLI in patients with MDS or AML relapsing after allogeneic stem cell transplantation.
Relapse after allogeneic stem cell transplantation is a major problem in patients with poor prognosis AML or MDS. Donor lymphocyte infusions alone re-induce remission in a minority of these patients, which may be the result of poor differentiation of the leukemic cells. The study drug 5-Aza is effective in AML and MDS.In addition to direct cytotoxicity, it alters gene expression and induces differentiation of leukemic blast cells. Furthermore, DNA-demethylating treatment results in an induction of transcription and cell surface expression of formerly unexpressed KIRs (killer Ig-like receptors) in NK cells, which are involved in the specific recognition of leukemic target cells and who are able to generate a specific graft-versus leukemia effect. The increased expression of MHC class I and II molecules on the surface of the recipient's leukemic cells and the de novo expression of formerly silenced KIR genes in donor NK cells due to treatment with 5-Aza may result in an increased susceptibility of myeloid leukemic cells to the allogeneic graft versus leukemia effect. Therefore, the graft-versus leukemia effect by donor lymphocyte infusions and NK cells from the original donor may be supported by additional therapy with 5-Azacitidine.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
5-Aza will be administered at doses of 100mg/m2 via subcutaneous injection over a period of 5 days. The total amount per treatment cycle, consisting of 5 days, is 500mg/m². Each treatment cycle is repeated every 28 days, with a treatment pause of 23 days between each 5-Aza cycle, to a total of 6 (optional 8 cycles) cycles. DLI will be transfused on day +34 with a total count of CD3+ cells of DLI 1-5x10E6CD3+/kg bodyweight. In absence of GvHD DLI transfusion is repeated on day +90 with DLI 1-5x10E7CD3+/kg bodyweight and on day +142 with DLI 1-5x10E8CD3+/kg bodyweight. Additional DLI may be given.
Universitaetsklinik Heidelberg, Medizinische Klinik und Poliklinik V
Heidelberg, Baden-Wurttemberg, Germany
Bone Marrow Transplantation Unit, University Hospital Hamburg-Eppendorf
Hamburg, Free and Hanseatic City of Hamburg, Germany
Klinikum der Johann-Wolfgang-Goethe Universität, Medizinische Klinik II
Frankfurt am Main, Hesse, Germany
Best response
Time frame: within the 6 months of treatment
Safety and Toxicity of 5-Azacitidine for patients relapsing after allo-SCT
Time frame: within 3 years
Response rate
Time frame: within 6 months
Duration of remissions
Time frame: within 3 years
Incidence of acute and chronic GvHD
Time frame: 3 years
Achievement of complete chimerism
Time frame: 6 month
Toxicity
Time frame: wtihin 3 years
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Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf
Düsseldorf, North Rhine-Westphalia, Germany
Universitaetsklinikum Dresden, Medizinische Klinik und Poliklinik I
Dresden, Saxony, Germany
Charite´-Campus Benjamin Franklin, Medizinische Klinik III
Berlin, State of Berlin, Germany