AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 3AMADEUSNCT04173533

Randomised Study of Oral Azacitidine vs Placebo Maintenance in AML or MDS Patients After Allo-SCT

A Phase 3 study testing Oral azacitidine in people with Acute Myeloid Leukemia and Myelodysplasia, run by University of Birmingham at 20 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will evaluate a new maintenance therapy with the aim of improving the outcome of patients with acute myeloid leukaemia (AML) and myelodysplasia (MDS) after stem cell transplantation. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Acute Myeloid Leukemia, Myelodysplasia
What is being tested?
Oral azacitidine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
326 participants
Where
20 sitesUnited Kingdom
Study dates
14 Jun 2019to 29 Apr 2026
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age ≥ 16 at the time of signing the informed consent form
  • Patients with a diagnosis of any of the below:
  • AML (CR1 or CR2) according to World Health Organization (WHO) classification;
  • Secondary AML (defined as previous history of MDS, antecedent hematological disease or chemotherapy exposure; CR1 or CR2); or
  • Advanced or high risk MDS with an IPSS-R of ≥3.5 (intermediate 3.5 or higher) including intermediate or high risk chronic myelomonocytic leukaemia (CMML) (e.g. CPSS int-2 or high risk) (as per IPSS-R)
  • undergoing allo-SCT using myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) preparative regimens, and with either peripheral blood or bone marrow as the source of hematopoietic stem cells.
Show all 32Show fewer
  • At the time of allo-SCT
  • No prior allo-SCT; and
  • No more than 1 antigen mismatch at HLA-A, -B, -C, -DRB1 or -DQB1 locus for either related or unrelated donor; and
  • No haplotype or cord blood donor; and
  • Bone marrow blast <5% for AML and <10% for MDS patients
  • Able to commence therapy between 42 to 84 days following allo-SCT
  • Post-transplant bone marrow
  • AML patients - blast count ≤ 5% confirmed within 28 days prior to starting study therapy
  • MDS patients - confirmation of CR post-transplant with blast count ≤ 5% in bone marrow
  • Adequate neutrophil and platelet engraftment within 14 days prior to starting study therapy defined as:
  • Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L on two consecutive testing without daily use of myeloid growth factor; and
  • Platelet ≥ 50 x 10^9/L on two consecutive testing without platelet transfusion within 1 week
  • Adequate organ function:
  • Serum aspartate aminotransferase (AST) and alanine transaminase (ALT) < 4 x upper limit of normal (ULN)
  • Serum bilirubin < 2 x ULN. Higher levels are acceptable if these can be attributed to active red blood cell (RBC) precursor destruction within the bone marrow (i.e., ineffective erythropoiesis) or Gilbert's syndrome
  • Serum creatinine < 2 x ULN
  • Adequate coagulation (Prothrombin time (PT) ≤ 15 seconds and partial thromboplastin time (PTT) ≤ 40 seconds)
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Patients with adequately controlled GVHD (defined as GVHD grade <II with concurrent use of corticosteroids equivalent of prednisone at a dose ≤ 0.5 mg/kg) can be included
  • Females of childbearing potential (FCBP) may participate, providing they meet the following conditions:
  • Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomised partner) or practice true abstinence throughout the study, and for 6 months following the last dose of study therapy and
  • Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at screening; and
  • Have a negative serum or urine (investigator's discretion) pregnancy test (sensitivity of at least 25 mIU/mL) within 72 hours prior to starting study therapy. This applies even if the subject practices complete abstinence from heterosexual contact.
  • Male patients with a female partner of childbearing potential must agree to the use of at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study and for 3 months following the last dose study therapy
  • Understand and voluntarily sign an informed consent from prior to any study related assessments or procedures being conducted
  • Able to adhere to the study visit schedule (i.e., clinic visits at the study sites are mandatory, unless noted otherwise for study visits) and other protocol requirements

Who cannot join

  • Use of any of the following after transplantation and prior to starting study therapy:
  • Any chemotherapy used for adjuvant therapy
  • Unlicensed investigational agents/therapies used within 28 days prior to starting study therapy
  • Azacitidine, decitabine or other hypomethylating agent (HMA)
  • Lenalidomide, thalidomide and pomalidomide used within 28 days prior to starting study therapy
  • Subjects who have undergone a haploidentical or cord blood transplant
Show all 22Show fewer
  • Active GVHD grade II or higher (acute GVHD Clinical Staging and Grading)
  • Concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg
  • Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV)
  • Active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
  • History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other GI disorder or defect that may interfere with the absorption, distribution, metabolism or excretion of the investigational medicinal products (IMPs) and/or predispose the subject to an increased risk of gastrointestinal toxicity prior to allo-SCT
  • Idiopathic thrombocytopenic purpura (ITP), disseminated intravascular coagulation, haemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP)
  • History of prior malignancies, except: lobular breast carcinoma in situ, fully resected basal cell or squamous cell carcinoma of skin or treated cervical carcinoma in situ, Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis (TNM) clinical staging system), previous MDS, CMML, myeloproliferative neoplasms (MPN) resulting in secondary AML. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent < 5 years previously will not be allowed.
  • Significant active cardiac disease within the previous 6 months, including:
  • New York Heart Association (NYHA) class III or IV congestive heart failure
  • Unstable angina or angina requiring surgical or medical intervention; and/or
  • Myocardial infarction
  • Known or suspected hypersensitivity to azacitidine or mannitol
  • Pregnant or lactating females
  • Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.
  • Any condition including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study
  • Any condition that confounds the ability to interpret data from the study

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

United Kingdom20 sites

  • The Queen Elizabeth Hospital

    Birmingham

  • University Hospital Bristol

    Bristol

  • Addenbrooke's Hospital

    Cambridge

  • University Hospital of Wales

    Cardiff

  • Queen Elizabeth University Hospital

    Glasgow

  • St. James's University Hospital

    Leeds

  • Leicester Royal Infirmary

    Leicester

  • Clatterbridge Cancer Centre

    Liverpool

  • Hammersmith Hospital

    London

  • King's College Hospital

    London

  • St Bartholomew's Hospital

    London

  • The Royal Marsden Hospital

    London

  • University College London Hospitals

    London

  • Manchester Royal Infirmary

    Manchester

  • The Christie Hospital

    Manchester

  • Freeman Hospital

    Newcastle

  • Nottingham City Hospital

    Nottingham

  • Churchill Hospital

    Oxford

  • Derriford Hospital

    Plymouth

  • Royal Hallamshire Hospital

    Sheffield

Other trials in United Kingdom

About this study

Official title: A Double-Blind, Phase III, Randomised Study to Compare the Efficacy and Safety of Oral Azacitidine (CC-486) Versus Placebo in Subjects With Acute Myeloid Leukaemia or Myelodysplastic Syndromes as Maintenance After Allogeneic Haematopoietic Stem Cell Transplantation

This study will evaluate a new maintenance therapy with the aim of improving the outcome of patients with acute myeloid leukaemia (AML) and myelodysplasia (MDS) after stem cell transplantation.

Read the detailed description

This is a prospective, two arm, double-blind, phase III clinical trial in adult patients with acute myeloid leukaemia (AML) and myelodysplasia (MDS) who have undergone an allogeneic stem cell transplant (allo-SCT) and are randomised to receive oral azacitidine or placebo upon engraftment for up to 12 months as maintenance therapy. Patients will be stratified by type of transplant (myeloablative/reduced intensity, age (<60/≥ 60 years) and donor type (sibling/unrelated)).

Being tested
Oral azacitidine, Matched placebo
Medical subject headings
Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral azacitidineDrug

    Also called CC-486

    Oral azacitidine (CC-486) 200 mg tablet

  • Matched placeboDrug

    Also called Oral azacitidine matched placebo

    Oral azacitidine (CC-486) matched placebo tablet

Study groups in NCT04173533
Study groupRoleWhat they receive
Control GroupPlacebo comparatorOral azacitidine (CC-486) matched placebo once daily for first 14 days of each 28 day cycle
Receives: Drug: Matched placebo
Experimental GroupExperimentalOral azacitidine (CC-486) 200 mg once daily for first 14 days of each 28 day cycle
Receives: Drug: Oral azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Relapse free survival (RFS)

    To determine RFS at one year from randomisation of oral azacitidine compared with placebo in patients undergoing allo-SCT for AML/MDS

    Measured: 12 months

Secondary outcomes (8)

  1. Overall survival (OS)

    OS at one and two years from randomisation of oral azacitidine compared with placebo

    Measured: 12 and 24 months

  2. Cumulative incidence of relapse (CIR)

    CIR at one and two years after treatment comparing oral azacitidine with placebo

    Measured: 12 and 24 months

  3. Non-relapse mortality (NRM)

    NRM at 100 days and 12 months after treatment comparing oral azacitidine with placebo

    Measured: Day 100 and 12 months

  4. Incidence of acute and chronic graft-versus-host disease (GVHD)

    Incidence of acute and chronic GVHD comparing oral azacitidine with placebo

    Measured: 24 months

  5. Time to early treatment discontinuation

    Time to early treatment discontinuation comparing oral azacitidine with placebo

    Measured: 24 months

  6. Safety (adverse events)

    Number of patients with adverse events on oral azacitidine compared with placebo

    Measured: 24 months

  7. Quality of Life (EORTC-QLQ-C30 and EQ-5D)

    QoL will be measured to compare oral azacitidine with placebo

    Measured: 24 months

  8. GVHD-free and relapse-free survival (GRFS)

    GRFS defined as time from date of randomisation to date of first event or death

    Measured: 12 and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2019
  2. Study start14 Jun 2019
  3. Primary completion29 Apr 2026
  4. Study completion29 Apr 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
326 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04173533
Sponsor's protocol ID
RG_18-048
Acronym
AMADEUS
Status last verified
Aug 2026
First submitted
20 Nov 2019
Last updated
14 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oral azacitidine in people with Acute Myeloid Leukemia and Myelodysplasia, run by University of Birmingham at 20 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relapse free survival (RFS) (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04173533.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
AMADEUS Clinical Trial NCT04173533 | AzTrials