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

Phase 2
Completed
Conditions
Myelodysplastic Syndrome
Acute Myelocytic Leukemia
Interventions
Registration Number
NCT01462578
Lead Sponsor
Technische Universität Dresden
Brief Summary

Assessment of efficacy of azacitidine to prevent a relapse

Detailed Description

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
93
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AzacytidineAzacitidineAzacytidine injection: 75 mg/m²/d, subcutaneous
Primary Outcome Measures
NameTimeMethod
Number of patients with hematological relapse 6 months after start of treatment with azacitidin6 months after end of treatment
Secondary Outcome Measures
NameTimeMethod
Rate of changes of methylation in CD34+ cells2 years follow-up after treatment
Number of occurrence or exacerbation of clinical relevant acute or chronic GvHD2 years follow-up after treatment
Relapse-free survival and overall survival12, 24 and 30 months after start of treatment

Relapse-free survival and overall survival 12, 24 and 30 months after start of treatment

Number of patients with infectious SAEs (rate of SAE)2 years follow-up after treatment

Trial Locations

Locations (11)

Klinikum Chemnitz (Küchwald)

🇩🇪

Chemnitz, Germany

Universitätsklinikum Bonn

🇩🇪

Bonn, Germany

Universitätsklinikum Heidelberg, Medizinische Klinik, Abt. Innere Medizin V

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Heidelberg, Germany

Klinikum der J. W. Goethe-Universität, Medizinische Klinik II Hämatologie / Onkologie

🇩🇪

Frankfurt am Main, Germany

Klinikum rechts der Isar der TU München, III. Med. Klinik und Poliklinik

🇩🇪

München, Germany

Universitätsklinikum Essen, Klinik für Hämatologie (Westdeutsches Tumorzentrum)

🇩🇪

Essen, Germany

Charité Campus Benjamin Franklin

🇩🇪

Berlin, Germany

Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I

🇩🇪

Dresden, Germany

Universitätsklinikum Freiburg

🇩🇪

Freiburg, Germany

LMU München, Klinikum Großhadern, Med. Klinik III

🇩🇪

München, Germany

Universitätsklinikum Münster, Innere Medizin A - KMT-Zentrum

🇩🇪

Münster, Germany

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