Safety Study of 5-Azacitidine and Standard Donor Lymphocyte Infusion (DLI) to Treat Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) Relapsing After Allogeneic Stem Cell Transplantation
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.
Acute Myeloid Leukemia
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase-II Trial to Assess the Efficacy and Toxicity of 5-Azacitidine in Addition to Standard DLI for the Treatment of Patients With AML or MDS Relapsing After Allogeneic Stem Cell Transplantation|
- Best response [ Time Frame: within the 6 months of treatment ] [ Designated as safety issue: No ]
- Safety and Toxicity of 5-Azacitidine for patients relapsing after allo-SCT [ Time Frame: within 3 years ] [ Designated as safety issue: Yes ]
- Response rate [ Time Frame: within 6 months ] [ Designated as safety issue: No ]
- Duration of remissions [ Time Frame: within 3 years ] [ Designated as safety issue: No ]
- Incidence of acute and chronic GvHD [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- Achievement of complete chimerism [ Time Frame: 6 month ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: wtihin 3 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2008|
|Study Completion Date:||August 2011|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
5-Azacitidine in addition to standard donor lymphocyte infusions.
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.
Other Name: Vidaza
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.
|Universitaetsklinik Heidelberg, Medizinische Klinik und Poliklinik V|
|Heidelberg, Baden-Wuertemberg, Germany, 69120|
|Klinikum der Johann-Wolfgang-Goethe Universität, Medizinische Klinik II|
|Frankfurt, Hessen, Germany, 60590|
|Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf|
|Duesseldorf, NW, Germany, 40225|
|Universitaetsklinikum Dresden, Medizinische Klinik und Poliklinik I|
|Dresden, Sachsen, Germany, 01307|
|Charite´-Campus Benjamin Franklin, Medizinische Klinik III|
|Berlin, Germany, 01220|
|Bone Marrow Transplantation Unit, University Hospital Hamburg-Eppendorf|
|Hamburg, Germany, 20246|
|Principal Investigator:||Guido Kobbe, PD Dr.||Department of Hematology, Oncology and Clinical Immunology|