NCT00795548

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Heinrich-Heine University, Duesseldorf · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Myelodysplastic Syndrome
• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	5-Azacitidine	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.

Timeline

• Start date: 2008-11-01
• Primary completion: 2010-10-01
• Completion: 2011-08-01
• First posted: 2008-11-21
• Last updated: 2012-01-23

Locations

6 sites across 1 country: Germany