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

Myelodysplastic Syndrome Clinical Trial

— RELAZA2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01462578
• Other study ID #: TUD-RELA02-048
• Secondary ID: 2010-022388-37VZ
• Status: Completed
• Phase: Phase 2
• Start date: September 2011
• Est. completion date: February 2021

Study information

• Verified date: November 2021
• Source: Technische Universität Dresden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Assessment of efficacy of azacitidine to prevent a relapse

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 information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: February 2021
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myelocytic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Azacitidine
Azacytidine injection: 75 mg/m²/d, subcutaneous; initial minimum 6 cycles; another 6 or 12 cycles according to MRD niveau; maximum 24 cycles

Locations

Country	Name	City	State
Germany	Charité Campus Benjamin Franklin	Berlin
Germany	Universitätsklinikum Bonn	Bonn
Germany	Klinikum Chemnitz (Küchwald)	Chemnitz
Germany	Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I	Dresden
Germany	Universitätsklinikum Essen, Klinik für Hämatologie (Westdeutsches Tumorzentrum)	Essen
Germany	Klinikum der J. W. Goethe-Universität, Medizinische Klinik II Hämatologie / Onkologie	Frankfurt am Main
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Universitätsklinikum Heidelberg, Medizinische Klinik, Abt. Innere Medizin V	Heidelberg
Germany	Klinikum rechts der Isar der TU München, III. Med. Klinik und Poliklinik	München
Germany	LMU München, Klinikum Großhadern, Med. Klinik III	München
Germany	Universitätsklinikum Münster, Innere Medizin A - KMT-Zentrum	Münster

Sponsors (1)

Lead Sponsor	Collaborator
Technische Universität Dresden

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Platzbecker U, Middeke JM, Sockel K, Herbst R, Wolf D, Baldus CD, Oelschlägel U, Mütherig A, Fransecky L, Noppeney R, Bug G, Götze KS, Krämer A, Bochtler T, Stelljes M, Groth C, Schubert A, Mende M, Stölzel F, Borkmann C, Kubasch AS, von Bonin M, Serve H, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with hematological relapse 6 months after start of treatment with azacitidin		6 months after end of treatment
Secondary	Number of occurrence or exacerbation of clinical relevant acute or chronic GvHD		2 years follow-up after treatment
Secondary	Number of patients with infectious SAEs (rate of SAE)		2 years follow-up after treatment
Secondary	Rate of changes of methylation in CD34+ cells		2 years follow-up after treatment
Secondary	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

External Links

•   Website Study Alliance Leukemia (coordinating study group)