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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

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
  Purpose

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 Intervention Phase
Myelodysplastic Syndrome
Acute Myeloid Leukemia
Drug: 5-Azacitidine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Heinrich-Heine University, Duesseldorf:

Primary Outcome Measures:
  • Best response [ Time Frame: within the 6 months of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 30
Study Start Date: November 2008
Study Completion Date: August 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00795548

Locations
Germany
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
Investigators
Principal Investigator: Guido Kobbe, PD Dr. Department of Hematology, Oncology and Clinical Immunology
  More Information

No publications provided

Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT00795548     History of Changes
Other Study ID Numbers: AZARELA_HHU_2007
Study First Received: November 20, 2008
Last Updated: January 20, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Heinrich-Heine University, Duesseldorf:
Myelodysplastic syndrome (MDS)
Acute myeloid leukemia (AML)
Stem cell transplantation
5-Azacitidine
Donor lymphocyte infusion
MDS or AML relapsed after stem cell transplantation

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Azacitidine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014