Assessment of efficacy of azacitidine to prevent a relapse

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

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.