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

Conditions

Acute Myelocytic Leukemia, Myelodysplastic Syndrome

Keywords

Neoplasms benign, malignant and unspecified, Acute myeloid leukemia, AML, Myelodysplastic syndrome, MDS

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

Platzbecker AS, Georgi JA, Middeke JM, Sockel K, Wehner R, Herbst RT, Wolf D, Baldus CD, Oelschlaegel U, Mütherig A, Fransecky L, Noppeney R, Bug G, Götze KS, Krämer A, Bochtler T, Stelljes M, Esseling E, Stölzel F, von Bonin M, Serve H, Hänel M, Dührsen U, Harig A, Müller-Tidow C, Schetelig J, Stasik S, Röllig C, Ehninger G, Kramer M, Schmitz M, Bornhäuser M, Platzbecker U, Thiede C.

2025-12-08

10.1182/blood.2025030816

Azacitidine for Pre-Emptive Treatment of Measurable-Residual Disease in MDS/AML Patients at High Risk of Hematological Relapse: Results of the Second Cohort of the RELAZA2 Trial

Uwe Platzbecker, Jan Moritz Middeke, Katja Sockel, Regina Herbst, Lars Fransecky et al. (32 authors)

Blood2019-11-136 citations

10.1182/blood-2019-129926

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.

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, Hänel M, Dührsen U, Schetelig J, Röllig C, Kramer M, Ehninger G, Bornhäuser M, Thiede C.

2018-11-12252 citations

10.1016/s1470-2045(18)30580-1

Minimal-Residual Disease Guided Treatment with Azacitidine in MDS/AML Patients at Imminent Risk of Relapse: Results of the Prospective RELAZA2 Trial

Uwe Platzbecker, Jan Moritz Middeke, Katja Sockel, Anke Mütherig, Regina Herbst et al. (27 authors)

Blood2017-12-077 citations

10.1182/blood.v130.suppl_1.565.565

Interventions

DRUGAzacitidine

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

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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.

Design outcomes

Primary

Measure	Time frame
Number of patients with hematological relapse 6 months after start of treatment with azacitidin	6 months after end of treatment

Secondary

Measure	Time frame	Description
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

Countries

Germany

Outcome results

None listed