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

NCT ID: NCT00795548

Last Updated: 2012-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2011-08-31

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.

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.

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

5-Azacitidine

5-Azacitidine in addition to standard donor lymphocyte infusions.

Group Type: EXPERIMENTAL

5-Azacitidine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Vidaza

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guido Kobbe, PD Dr.

Role: PRINCIPAL_INVESTIGATOR

Department of Hematology, Oncology and Clinical Immunology

Locations

Universitaetsklinik Heidelberg, Medizinische Klinik und Poliklinik V

Heidelberg, Baden-Wurttemberg, Germany

Bone Marrow Transplantation Unit, University Hospital Hamburg-Eppendorf

Hamburg, City state of Hamburg, Germany

Klinikum der Johann-Wolfgang-Goethe Universität, Medizinische Klinik II

Frankfurt am Main, Hesse, Germany

Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf

Düsseldorf, North Rhine-Westphalia, Germany

Universitaetsklinikum Dresden, Medizinische Klinik und Poliklinik I

Dresden, Saxony, Germany

Charite´-Campus Benjamin Franklin, Medizinische Klinik III

Berlin, State of Berlin, Germany

Countries

Germany

Other Identifiers

AZARELA_HHU_2007

Identifier Type: -

Identifier Source: org_study_id