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

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

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.