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

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

Assessment of efficacy of azacitidine to prevent a relapse

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome; Acute Myelocytic Leukemia
• Intervention / Treatment: Drug: Azacitidine

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 Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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®

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Relapse-free survival and overall survival 12, 24 and 30 months after start of treatment	12, 24 and 30 months after start of treatment

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Investigators: Principal Investigator: Uwe Platzbecker, Prof. Dr., Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I, 01307 Dresden

Publications and helpful links

General Publications

• 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.

Helpful Links

• Website Study Alliance Leukemia (coordinating study group)

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): February 1, 2021

Study Registration Dates

• First Submitted: June 22, 2011
• First Submitted That Met QC Criteria: October 28, 2011
• First Posted (Estimate): October 31, 2011

Study Record Updates

• Last Update Posted (Actual): November 15, 2021
• Last Update Submitted That Met QC Criteria: November 12, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: AML; MDS; Myelodysplastic syndrome; Acute myeloid leukemia; Neoplasms benign, malignant and unspecified
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: TUD-RELA02-048; 2010-022388-37 (EudraCT Number); VZ-MDS-PI-0245 (Other Identifier: Celgene)