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

NCT04173533 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: RG_18-048
• Study Type: interventional
• Target: 326
• Locations: 1 country
• Sites: 20

Brief 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.

Conditions

Acute Myeloid Leukemia; Myelodysplasia

Outcome Measures

Primary Outcomes (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

  12 months

Secondary Outcomes (8)

• Overall survival (OS)

  12 and 24 months

• Cumulative incidence of relapse (CIR)

  12 and 24 months

• Non-relapse mortality (NRM)

  Day 100 and 12 months

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

  24 months

• Time to early treatment discontinuation

  24 months

Study Arms (2)

Control Group

PLACEBO COMPARATOR

Oral azacitidine (CC-486) matched placebo once daily for first 14 days of each 28 day cycle

Drug: Matched placebo

Experimental Group

EXPERIMENTAL

Oral azacitidine (CC-486) 200 mg once daily for first 14 days of each 28 day cycle

Drug: Oral azacitidine

Interventions

Oral azacitidine DRUG

Oral azacitidine (CC-486) 200 mg tablet

Also known as: CC-486

Experimental Group

Matched placebo DRUG

Oral azacitidine (CC-486) matched placebo tablet

Also known as: Oral azacitidine matched placebo

Control Group

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (20)

The Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

University Hospital Bristol

Bristol, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

St. James's University Hospital

Leeds, United Kingdom

Location

Leicester Royal Infirmary

Leicester, United Kingdom

Location

Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

Hammersmith Hospital

London, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

St Bartholomew's Hospital

London, United Kingdom

Location

The Royal Marsden Hospital

London, United Kingdom

Location

University College London Hospitals

London, United Kingdom

Location

Manchester Royal Infirmary

Manchester, United Kingdom

Location

The Christie Hospital

Manchester, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Derriford Hospital

Plymouth, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts

Interventions

Azacitidine; cc-486

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Charles Craddock

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: November 22, 2019
• Study Start: June 14, 2019
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (20)