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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

Phase 2
18 Years
Not Enrolling
Myelodysplastic Syndrome, Acute Myeloid Leukemia

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Trial Information

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

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

Inclusion Criteria:

- Primary and secondary MDS, AML after MDS, and de novo AML relapsing after
allogeneic stem cell transplantation

- Eligibility for Donor Lymphocyte Infusions

- Performance status according to the WHO scale: 0, 1 or 2.

- Adequate renal and liver function: bilirubin < 1.5 times the upper limit
of normal and a GFR > 50 ml/min

- Absence of severe cardiovascular disease, i.e., arrhythmias requiring chronic
treatment, congestive heart failure (NYHA Class III or IV) or symptomatic
ischemic heart disease, where New-York Heart Association (NYHA)

- HIV negative and HBs-Ag negative.

- Absence of active uncontrolled infection (Septicaemia).

- No prior history or current evidence of central nervous system and psychiatric
disorders requiring hospitalization.

- Age at least 18 years.

- Negative pregnancy test for women with reproductive potential.

- Signed written informed consent must be given according to national/local

Exclusion Criteria:

- Have malignant hepatic tumors.

- Severe liver dysfunction CHILD B and C.

- Renal insufficiency with a GFR < 50 ml/min

- Radiation therapy, chemotherapy, or cytotoxic therapy, given to treat conditions
other than MDS, AML or applied for conditioning prior allogeneic stemcell

- Psychiatric illness that would prevent granting of informed consent.

- Treatment with androgenic hormones during the previous 14 days prior Day 1.

- Active viral infection with known human immunodeficiency virus (HIV) or viral
Hepatitis B or C.

- Hypersensitivity to Mannitol or 5-Azacitidine.

- Treatment with other investigational drugs following relapse after allogeneic
stemcell transplantation or ongoing adverse events from previous treatment with
investigational drugs regardless of time period.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Best response

Outcome Time Frame:

within the 6 months of treatment

Safety Issue:


Principal Investigator

Guido Kobbe, PD Dr.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Department of Hematology, Oncology and Clinical Immunology


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

November 2008

Completion Date:

August 2011

Related Keywords:

  • Myelodysplastic Syndrome
  • Acute Myeloid Leukemia
  • Myelodysplastic syndrome (MDS)
  • Acute myeloid leukemia (AML)
  • Stem cell transplantation
  • 5-Azacitidine
  • Donor lymphocyte infusion
  • MDS or AML relapsed after stem cell transplantation
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia