RELAZA2: Treatment of Patients With Myelodysplastic Syndrome or Acute Myelocytic Leukemia With an Impending Hematological Relapse With Azacitidine (Vidaza)

Sponsor

Technische Universität Dresden (Other)

Overall Status

Completed

CT.gov ID

NCT01462578

Collaborator

(none)

Enrollment

Locations

Arm

113.1

Duration (Months)

8.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Assessment of efficacy of azacitidine to prevent a relapse

Condition or Disease	Intervention/Treatment	Phase
Acute Myelocytic Leukemia Myelodysplastic Syndrome	Drug: Azacitidine	Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

93 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2011

Actual Primary Completion Date :

Aug 1, 2018

Actual Study Completion Date :

Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azacytidine Azacytidine injection: 75 mg/m²/d, subcutaneous	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 Other Names: Vidaza®

Arm

Intervention/Treatment

Experimental: Azacytidine

Azacytidine injection: 75 mg/m²/d, subcutaneous

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

Other Names:

Vidaza®

Outcome Measures

Primary Outcome Measures

Number of patients with hematological relapse 6 months after start of treatment with azacitidin [6 months after end of treatment]

Secondary Outcome Measures

Number of occurrence or exacerbation of clinical relevant acute or chronic GvHD [2 years follow-up after treatment]
Number of patients with infectious SAEs (rate of SAE) [2 years follow-up after treatment]
Rate of changes of methylation in CD34+ cells [2 years follow-up after treatment]
Relapse-free survival and overall survival [12, 24 and 30 months after start of treatment]
Relapse-free survival and overall survival 12, 24 and 30 months after start of treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

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