Clinical trial NCT01462578: Treatment of Patients With Myelodysplastic Syndrome or Acute Myelocytic Leukemia With an Impending Hematological Relapse With Azacitidine (Vidaza)
Official title: Treatment of Patients With MDS or AML With an Impending Hematological Relapse With Azacitidine (Vidaza)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myelocytic Leukemia
Myelodysplastic Syndrome
Keywords: Neoplasms benign, malignant and unspecified
Acute myeloid leukemia
AML
Myelodysplastic syndrome
MDS
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
First posted: 2011-10-31
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility 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

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.

Primary outcomes:
measure: Number of patients with hematological relapse 6 months after start of treatment with azacitidin
timeFrame: 6 months after end of treatment
Secondary outcomes:
measure: Number of occurrence or exacerbation of clinical relevant acute or chronic GvHD
timeFrame: 2 years follow-up after treatment
measure: Number of patients with infectious SAEs (rate of SAE)
timeFrame: 2 years follow-up after treatment
measure: Rate of changes of methylation in CD34+ cells
timeFrame: 2 years follow-up after treatment
measure: Relapse-free survival and overall survival
timeFrame: 12, 24 and 30 months after start of treatment
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz (Küchwald)
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Hämatologie (Westdeutsches Tumorzentrum)
city: Frankfurt am Main
country: Germany
facility: Klinikum der J. W. Goethe-Universität, Medizinische Klinik II Hämatologie / Onkologie
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Medizinische Klinik, Abt. Innere Medizin V
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München, III. Med. Klinik und Poliklinik
city: München
country: Germany
facility: LMU München, Klinikum Großhadern, Med. Klinik III
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Innere Medizin A - KMT-Zentrum
Study officials:
affiliation: Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I, 01307 Dresden
name: Uwe Platzbecker, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Platzbecker U, Middeke JM, Sockel K, Herbst R, Wolf D, Baldus CD, Oelschlagel U, Mutherig A, Fransecky L, Noppeney R, Bug G, Gotze KS, Kramer A, Bochtler T, Stelljes M, Groth C, Schubert A, Mende M, Stolzel F, Borkmann C, Kubasch AS, von Bonin M, Serve H, Hanel M, Duhrsen U, Schetelig J, Rollig C, Kramer M, Ehninger G, Bornhauser M, Thiede C. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018 Dec;19(12):1668-1679. doi: 10.1016/S1470-2045(18)30580-1. Epub 2018 Nov 12.