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Sponsored by: |
Heinrich-Heine University, Duesseldorf |
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Information provided by: | Heinrich-Heine University, Duesseldorf |
ClinicalTrials.gov Identifier: | NCT00795548 |
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 |
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Myelodysplastic Syndrome Acute Myeloid Leukemia |
Drug: 5-Azacitidine |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
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 |
Estimated Enrollment: | 30 |
Study Start Date: | November 2008 |
Estimated Study Completion Date: | December 2013 |
Estimated Primary Completion Date: | November 2011 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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5-Azacitidine: Experimental
5-Azacitidine in addition to standard donor lymphocyte infusions.
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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. |
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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Primary and secondary MDS, AML after MDS, and de novo AML relapsing after allogeneic stem cell transplantation
Exclusion Criteria:
- Have malignant hepatic tumors.
Contact: Guido Kobbe, PD Dr. | 0049-211-8117720 | Kobbe@med.uni-duesseldorf.de |
Contact: Akos Czibere, Dr. | 0049-211-8117720 | Akos.Czibere@med.uni-duesseldorf.de |
Germany | |
Bone Marrow Transplantation Unit, University Hospital Hamburg-Eppendorf | Not yet recruiting |
Hamburg, Germany, 20246 | |
Contact: Nikolaus Kroeger, Prof.Dr. 0049-40-428035864 | |
Principal Investigator: Nikolaus Kroeger, Prof. Dr. | |
Germany, NW | |
Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf | Recruiting |
Duesseldorf, NW, Germany, 40225 | |
Contact: Guido Kobbe, PD Dr. 0049-211-8117720 Kobbe@med.uni-duesseldorf.de | |
Contact: Akos Czibere, Dr. 0049-211-8117720 Akos.Czibere@med.uni-duesseldorf.de | |
Principal Investigator: Guido Kobbe, PD Dr. | |
Sub-Investigator: Akos Czibere, Dr. |
Principal Investigator: | Guido Kobbe, PD Dr. | Department of Hematology, Oncology and Clinical Immunology |
Responsible Party: | Heinrich-Heine University, Duesseldorf, Dep.of Hematology, Oncology, Clinical Immunology ( Heinrich-Heine University represented by Coordinating Investigator PD Dr. Guido Kobbe ) |
Study ID Numbers: | AZARELA_HHU_2007 |
Study First Received: | November 20, 2008 |
Last Updated: | November 20, 2008 |
ClinicalTrials.gov Identifier: | NCT00795548 |
Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Myelodysplastic syndrome (MDS) Acute myeloid leukemia (AML) Stem cell transplantation |
5-Azacitidine Donor lymphocyte infusion MDS or AML relapsed after stem cell transplantation |
Myelodysplastic syndromes Precancerous Conditions Hematologic Diseases Myelodysplastic Syndromes Myelodysplasia Acute myelogenous leukemia Leukemia, Myeloid |
Leukemia, Myeloid, Acute Leukemia Preleukemia Azacitidine Bone Marrow Diseases Acute myelocytic leukemia |
Antimetabolites Neoplasms Antimetabolites, Antineoplastic Pathologic Processes Disease Neoplasms by Histologic Type |
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Therapeutic Uses Syndrome Enzyme Inhibitors Pharmacologic Actions |