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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00795548
Recruitment Status : Completed
First Posted : November 21, 2008
Last Update Posted : January 23, 2012
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf

Brief 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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome Acute Myeloid Leukemia Drug: 5-Azacitidine Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : November 2008
Actual Primary Completion Date : October 2010
Actual Study Completion Date : August 2011

Arm Intervention/treatment
Experimental: 5-Azacitidine
5-Azacitidine in addition to standard donor lymphocyte infusions.
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

Primary Outcome Measures :
  1. Best response [ Time Frame: within the 6 months of treatment ]

Secondary Outcome Measures :
  1. Safety and Toxicity of 5-Azacitidine for patients relapsing after allo-SCT [ Time Frame: within 3 years ]
  2. Response rate [ Time Frame: within 6 months ]
  3. Duration of remissions [ Time Frame: within 3 years ]
  4. Incidence of acute and chronic GvHD [ Time Frame: 3 years ]
  5. Achievement of complete chimerism [ Time Frame: 6 month ]
  6. Toxicity [ Time Frame: wtihin 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00795548

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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
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
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Principal Investigator: Guido Kobbe, PD Dr. Department of Hematology, Oncology and Clinical Immunology

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Responsible Party: Heinrich-Heine University, Duesseldorf Identifier: NCT00795548     History of Changes
Other Study ID Numbers: AZARELA_HHU_2007
First Posted: November 21, 2008    Key Record Dates
Last Update Posted: January 23, 2012
Last Verified: January 2012
Keywords provided by Heinrich-Heine University, Duesseldorf:
Myelodysplastic syndrome (MDS)
Acute myeloid leukemia (AML)
Stem cell transplantation
Donor lymphocyte infusion
MDS or AML relapsed after stem cell transplantation
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors