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

Heinrich-Heine University, Duesseldorf

Status and phase

Completed

Phase 2

Conditions

Myelodysplastic Syndrome

Acute Myeloid Leukemia

Treatments

Drug: 5-Azacitidine

Study type

Interventional

Funder types

Other

Identifiers

NCT00795548

AZARELA_HHU_2007

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 regulations.

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 transplantation.
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.