Treatment of Patients With Myelodysplastic Syndrome or Acute Myelocytic Leukemia With an Impending Hematological Relapse With Azacitidine (Vidaza)

Study Overview
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Brief Summary
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Assessment of efficacy of azacitidine to prevent a relapse

Detailed Description
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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 (<80%) after allogeneic related or unrelated HSCT in CD34+ or CD117+ MDS or AML or increase in the AML-specific molecular markers in the quantitative PCR for t(6,9), NPM1+ AML >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 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

Official Title
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Treatment of Patients With MDS or AML With an Impending Hematological Relapse With Azacitidine (Vidaza)

Conditions
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Acute Myelocytic Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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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 Treatment: MDS or AML without haematological relapse (blasts <5% in the bone marrow), and decrease of CD34 donor chimerism (<80%) after allogeneic related or unrelated HSCT in CD34+ or CD117+ MDS or AML or increase in the AML-specific molecular marker in the quantitative PCR for t(6,9), NPM1+ AML >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) 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: post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum FSH >40 U/ml) postoperative (6 weeks after hysterectomy with or without bilateral ovariectomy ) 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 sexual abstinence during study treatment and up to 1 year after completion of therapy 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: sexual abstinence State post-vasectomy 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azacytidine<br>Azacytidine injection: 75 mg/m²/d, subcutaneous | Drug: Azacitidine<br>* Azacytidine injection: 75 mg/m²/d, subcutaneous; initial minimum 6 cycles; another 6 or 12 cycles according to MRD niveau; maximum 24 cycles<br>* Other names: Vidaza®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with hematological relapse 6 months after start of treatment with azacitidin |  | 6 months after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of occurrence or exacerbation of clinical relevant acute or chronic GvHD |  | 2 years follow-up after treatment | 
| Number of patients with infectious SAEs (rate of SAE) |  | 2 years follow-up after treatment | 
| Rate of changes of methylation in CD34+ cells |  | 2 years follow-up after treatment | 
| Relapse-free survival and overall survival | Relapse-free survival and overall survival 12, 24 and 30 months after start of treatment | 12, 24 and 30 months after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasms benign, malignant and unspecified, Acute myeloid leukemia, AML, Myelodysplastic syndrome, MDS