Patients with AML or MDS >= 18 years of age after conventional chemotherapy or stem cell transplantation with significant residual disease or an increase of MRD (e.g. t(6,9), NPM1 or CD34+ or CD117+ in case of PBSC Tx) MedDRA version: 20.0 Level: LLT Classification code 10060557 Term: Acute myelocytic leukemia System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Vidaza®
Product Name: Vidaza
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: AZACITIDINE
CAS Number: 320-67-2
Concentration unit: mg milligram(s)
Concentratio
Sponsors
Technische Universität Dresden
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Screening: - signed informed consent - Age =18 years - patients with MDS or AML after conventional chemotherapy or allogeneic HSCT and positive molecular marker such as t(6,9), NPM1 pos. or CD34+ or CD117+ in the case of an allogeneic HSCT (CD34+/CD117+ positivity of blasts = 10% at any time prior to HSCT) Treatment: - MDS or AML without haematological relapse (blasts 1% after conventional chemotherapy or allogeneic HSCT or - persistence of the (above) MRD levels >1% (relative to the reference gene) after conventional chemotherapy or allogeneic HSCT - leukocytes > 3 Gpt/l and platelets >75 Gpt/l (transfusion independent) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 93 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 93
Exclusion criteria
Exclusion criteria: - Known history of hypersensitivity to any of the drugs used or their constituents or to drugs with similar chemical structure, - Participation of the patient in another clinical trial within the last 4 weeks before the inclusion - addiction or other disorders that do not allow the concerned person, to assess the nature and scope and possible consequences in the clinical investigation - pregnant or breast feeding women - women of childbearing potential, except women who meet the following criteria: o post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum FSH> 40 U/ml) o postoperative (6 weeks after hysterectomy with or without bilateral ovariectomy) o regular and proper use of a contraceptive method with error rate <1% per year (e.g., implants, depot injections, oral contraceptives, intrauterine device, IUD) during study treatment and up to 1 year after completion of therapy o sexual abstinence during study treatment and up to 1 year after completion of therapy o Vasectomy of the partner - Men who do not use one of the following types of effective contraception during study treatment and up to 1 year after completion of therapy: o sexual abstinence o State post-vasectomy o Condom - Evidence that the participating person is not expected to comply with the protocol (such as lack of cooperation) - Uncontrolled active infection - Severe hepatic impairment (AST and ALT may not exceed three times the normal) or liver cirrhosis or malignant liver tumor - Dialysis dependent renal dysfunction - Known severe congestive heart failure, incidence of clinically unstable cardiac or pulmonary disease These criteria are not for the screening phase up to a known allergic reaction to azacitidine or intolerance to apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Analysis of the effectiveness of azacitidine 6 months after start of therapy to prevent a hematological relapse in MDS or AML patients with significant residuals or an increase of minimal residual disease (MRD) which is defined as - decrease of CD34 donor chimerism (1% (ratio to reference gene) after conventional chemotherapy or allogeneic HSCT or - Persistence of the (above) MRD level >1% after conventional chemotherapy or allogeneic HSCT;Secondary Objective: - tolerance of azacitidine - quality of the response of the MRD (major vs. minor) and the relapse-free survival and overall survival 12, 24 and 30 months after starting treatment with azacitidine - Modulation of CD34+, NK- and T- cells of MDS and AML patients by azacitidine - Investigation of predictive molecular markers - Analysis of immunomodulatory regulators;Primary end point(s): Rate of treatment success (relapsed patients after 6 months of treatment);Timepoint(s) of evaluation of this end point: after 6 months after start of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 30 months after start of therapy with Azacitidin;Secondary end point(s): - Occurrence or exacerbation of a clinical relevant acute or chronic GvHD - Rate of infectious SAEs - Qualitative and quantitative changes by azacitidine in NK- and T-cells - Change of methylation in CD34+ cells - Major / minor response or relapse-free survival and overall survival 12, 24 and 30 months after starting treatment with azacitidine - Frequency of PD-1 on T cells and PD-L1 on blasts - Mutation load of selected genes (eg DNMT3A, TET2) and their influence on the response | — |
Countries
Germany
Contacts
Public Contactcoordinating investigator
Medizinische Fakultät der TU Dresden, Medizinische Klinik und Poliklinik I
Outcome results
None listed