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

• ClinicalTrials.gov Identifier: NCT01462578
• Recruitment Status: Completed
• First Posted: October 31, 2011
• Last Update Posted: November 15, 2021
• Sponsor: Technische Universität Dresden
• Information provided by (Responsible Party): Technische Universität Dresden

Tracking Information

• First Submitted Date: June 22, 2011
• First Posted Date: October 31, 2011
• Last Update Posted Date: November 15, 2021
• Study Start Date: September 2011
• Actual Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 28, 2011): Number of patients with hematological relapse 6 months after start of treatment with azacitidin [ Time Frame: 6 months after end of treatment ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 28, 2011)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acute Myelocytic Leukemia
• Myelodysplastic 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

Other Name: Vidaza®

Study Arms

Experimental: Azacytidine

Azacytidine injection: 75 mg/m²/d, subcutaneous

Intervention: Drug: Azacitidine

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 13, 2017): 93
• Original Estimated Enrollment (submitted: October 28, 2011): 53
• Actual Study Completion Date: February 2021
• Actual Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01462578
• Other Study ID Numbers: TUD-RELA02-048; 2010-022388-37 ( EudraCT Number ); VZ-MDS-PI-0245 ( Other Identifier: Celgene )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Technische Universität Dresden
• Original Responsible Party: Dresden University of Technology
• Current Study Sponsor: Technische Universität Dresden
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Technische Universität Dresden
• Verification Date: November 2021