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 study has been completed.
Sponsor:
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier:
NCT00795548
First received: November 20, 2008
Last updated: January 20, 2012
Last verified: January 2012

November 20, 2008
January 20, 2012
November 2008
October 2010   (final data collection date for primary outcome measure)
Best response [ Time Frame: within the 6 months of treatment ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00795548 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 [ Designated as safety issue: Yes ]
  • Achievement of complete chimerism [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: wtihin 3 years ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Myelodysplastic Syndrome
  • Acute Myeloid Leukemia
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.

Other Name: Vidaza
Experimental: 5-Azacitidine
5-Azacitidine in addition to standard donor lymphocyte infusions.
Intervention: Drug: 5-Azacitidine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
August 2011
October 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00795548
AZARELA_HHU_2007
No
Heinrich-Heine University, Duesseldorf
Heinrich-Heine University, Duesseldorf
Not Provided
Principal Investigator: Guido Kobbe, PD Dr. Department of Hematology, Oncology and Clinical Immunology
Heinrich-Heine University, Duesseldorf
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP